記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Gastric cancer (GC) in younger patients often exhibits aggressive behavior and a poorer prognosis than that in older patients. Although the clinical differences may stem from oncogenic gene variations, it is unclear whether genetic differences exist between these groups. This study compared the genetic profiles of early- and late-onset GC and evaluated their impact on treatment outcomes. METHODS: We analyzed genetic data from 1284 patients with GC in the Japanese nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, comparing early-onset (≤ 39 years; n = 143) and late-onset (≥ 65 years; n = 1141) groups. The influence of TP53 mutations on the time to treatment failure (TTF) with platinum-based chemotherapy and the sensitivity of cancer cells with different TP53 mutation sites to oxaliplatin were assessed in vitro. RESULTS: Early- and late-onset GC showed distinct genetic profiles, with fewer neoantigen-associated genetic changes observed in early-onset cases. In particular, TP53 has distinct mutation sites; R175H and R273 mutations are more frequent in early- and late-onset GC, respectively. The R175H mutation showed higher sensitivity to oxaliplatin in vitro, consistent with the longer TTF in early-onset patients (17.3 vs. 7.0 months, p = 0.013) when focusing on the patients with TP53 mutations. CONCLUSION: Genomic differences, particularly in TP53 mutation sites, between early- and late-onset GC support the need for age-specific treatment strategies.

DOI： 10.1002/cam4.70793

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Exosomes play an important role in regulating physiological processes and mediating the systemic dissemination of various types of cancer. We investigated the association of exosomal tetraspanins CD9, CD63, and CD81 in patients with ovarian cancer (OC). MATERIAL AND METHODS: We measured the plasma tetraspanins CD9, CD63, and CD81 by enzyme-linked immunosorbent assay in 91 patients who underwent treatment for OC between April 2018 and March 2024. Additionally, we analyzed clinical pathologic factors, chemotherapy response, and prognosis. RESULTS: In terms of stages, CD63 expression was significantly higher in patients with stage IV compared to those with stage I OC (p = 0.003). In terms of histological type, CD63 expression was significantly higher in high-grade serous carcinoma (HGSC) than in clear cell carcinoma (CCC) with OC (p = 0.009). Furthermore, CD63 levels were significantly higher in advanced-stage, HGSC than in patients with early-stage, non-HGSC and early-stage, HGSC OC (p = 0.045 and p = 0.002, respectively). In the Neoadjuvant chemotherapy (NAC) of 12 patients with OC assessed as having either a partial response (PR) or complete response (CR), CD63 was significantly decreased (p = 0.043), whereas perforin was significantly increased (p = 0.001). In the NAC of 16 patients with OC, CD63 of the response rate to chemotherapy tended to differ between the progressive disease (PD) and PR/CR groups (p = 0.056). A moderate inverse correlation was observed between CD63 and perforin levels (R = 0.638, R2 = 0.428, p = 0.008). CONCLUSIONS: CD63 could be a potential biomarker for all types of OC patients.

DOI： 10.1016/j.ejogrb.2025.01.011

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.gimo.2025.102987

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Patients with ovarian cancer, especially the high-grade serous ovarian cancer (HGSOC) subtype, face poor prognosis due to late diagnosis and treatment resistance. Owing to the high heterogeneity of HGSOC, identifying the origin of the disease and optimal treatments is difficult. Here, we characterized two primary immortalized human ovarian cell lines, human ovarian surface epithelium (HOSE)1C and HOSE2C, comparing their molecular profiling with representative HGSOC cells. We identified molecular features associated with normal and malignant phenotype of ovarian cells by applying single-cell transcriptomics, high-content image-based cell painting, and high-throughput drug testing. Our findings reveal distinct transcriptomic and morphological profiles for the two HOSEs, with a stromal phenotype. Moreover, their responses to the tumor microenvironment differ, exemplified by STAT1 and GREM1 upregulation in HOSE1C and HOSE2C, respectively. We identified selective activation of ERK/MEK targeted inhibitors in cancer cells compared to HOSEs. This study offers insights into the normal and malignant ovarian cells, shedding light on cancer development and drug responses.

DOI： 10.1016/j.omton.2024.200903

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Neurofibromatosis type 1 (NF1) presents with a broad spectrum of clinical manifestations, including an increased risk of tumor development and hypertension. Comprehensive data on genotype‒phenotype correlations in patients with NF1 are limited. Therefore, in this study, we aimed to elucidate the detailed genetic and clinical characteristics of NF1 in a hereditary tumor cohort. We performed sequencing and copy number assays in a clinical laboratory and analyzed the clinical data of 44 patients with suspected NF1. Germline pathogenic variants were detected in 36 patients (81.8%), and 20.7% of the variants were novel. Notably, 40.0% of adult patients presented with malignancies; female breast cancer occurred in 20.0% of patients, which was a higher rate than that previously reported. Hypertension was observed in 30.6% of the adult patients, with one patient experiencing sudden death and another developing pheochromocytoma. Three patients with large deletions in NF1 exhibited prominent cutaneous, skeletal, and neurological manifestations. These results highlight the importance of regular surveillance, particularly for patients with malignancies and hypertension. Our findings provide valuable insights for genetic counseling and clinical management, highlighting the multiple health risks associated with NF1 and the need for comprehensive and multidisciplinary care.

DOI： 10.1038/s41439-024-00299-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

(1) Background: The number of patients with cancer undergoing cancer genome profiling is increasing; however, it remains unclear how accurately they understand the details of the tests and treatments. This study aimed to clarify the awareness of cancer genome profiling tests among patients with cancer who visited cancer genome medical clinics. (2) Methods: A questionnaire survey was conducted on awareness, anxiety, sources of information, and psychological states concerning cancer genome profiling tests. (3) Results: In total, 265 patients with cancer (117 men, 142 women, 6 no response, average age of 58.29 ± 11.9 years) were included in the study, of which 218 (82.3%) were aware of the term "cancer genomic medicine" and 90 (34.0%) were aware of its details. Thus, only a few respondents understood that cancer genome profiling tests facilitate the discovery of secondary findings and of genes associated with hereditary tumors. Regarding their psychological state when visiting the cancer genome clinic, the respondents were anxious about standard treatment and prognosis limits. (4) Conclusions: From the viewpoint of advance care planning, we suggest that medical professionals build a support system that links palliative care and cancer treatment and coordinates genetic counseling at an early stage.

DOI： 10.3390/clinpract14050166

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We surveyed the status of the secondary finding (SF) disclosure in comprehensive genome profiling (CGP) in 2020. The situation has changed: increase in the number of hospitals that provide CGP, an update to the Comprehensive Tumor Genomic Profiling: Materials for Review of Secondary Findings (CTGPMRSF), and the addition of a liquid biopsy test, FoundationOne® Liquid CDx (F1L). Moreover, the actual situation was unclear because the 2020 survey did not include all designated and cooperative hospitals. Herein, we conducted a questionnaire survey of all designated-core, designated, and cooperative hospitals to identify the current status and challenges concerning SF in the CGP in 2022. A total of 82.1% of the hospitals responded and 77.7% of the response was from cooperative hospitals. Approximately 80% of the hospitals used CTGPMRSF. SF disclosure, confirmatory test implementation, and SF confirmation rates were 12.4%, 31.6%, and 46.6% for FoundationOne® CDx (F1CDx), respectively, and 6.8%, 31.8%, and 70.7% for F1L, respectively. The implementation rate of the confirmatory test was substantially higher in hospitals with genetic experts and in hospitals that could conduct confirmatory tests on the same day. Our survey provides insight into how SF is handled in Japan. The percentage of cases leading to confirmatory tests has gradually increased, although challenges such as insurance coverage limitations and varied understanding of SF among patients and healthcare providers persist. With the increasing use of whole-genome analysis, our findings will provide valuable insights into establishing an effective SF disclosure system.

DOI： 10.1038/s10038-024-01294-x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Innovations in sequencing technology have led to the discovery of novel mutations that cause inherited diseases. However, many patients with suspected genetic diseases remain undiagnosed. Long-read sequencing technologies are expected to significantly improve the diagnostic rate by overcoming the limitations of short-read sequencing. In addition, Oxford Nanopore Technologies (ONT) offers adaptive sampling and computationally driven target enrichment technology. This enables more affordable intensive analysis of target gene regions compared to standard non-selective long-read sequencing. In this study, we developed an efficient computational workflow for target adaptive sampling long-read sequencing (TAS-LRS) and evaluated it through application to 33 genomes collected from suspected hereditary cancer patients. Our workflow can identify single nucleotide variants with nearly the same accuracy as the short-read platform and elucidate complex forms of structural variations. We also newly identified several SINE-R/VNTR/Alu (SVA) elements affecting the APC gene in two patients with familial adenomatous polyposis, as well as their sites of origin. In addition, we demonstrated that off-target reads from adaptive sampling, which is typically discarded, can be effectively used to accurately genotype common single-nucleotide polymorphisms (SNPs) across the entire genome, enabling the calculation of a polygenic risk score. Furthermore, we identified allele-specific MLH1 promoter hypermethylation in a Lynch syndrome patient. In summary, our workflow with TAS-LRS can simultaneously capture monogenic risk variants including complex structural variations, polygenic background as well as epigenetic alterations, and will be an efficient platform for genetic disease research and diagnosis.

DOI： 10.1038/s41525-024-00394-z

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記述言語：日本語   出版者・発行元：日本レックリングハウゼン病学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In Japan, comprehensive genomic profiling (CGP) tests have been reimbursed under the national health care system for solid cancer patients who have finished standard treatment. More than 50,000 patients have taken the test since June 2019. We performed a nation-wide questionnaire survey between March 2021 and July 2022. Questionnaires were sent to 80 designated Cancer Genomic Medicine Hospitals. Of the 933 responses received, 370 (39.7%) were web based and 563 (60.3%) were paper based. Most patients (784, 84%) first learned about CGP tests from healthcare professionals, and 775 (83.1%) gave informed consent to their treating physician. At the time of informed consent, they were most worried about test results not leading to novel treatment (536, 57.4%). On a scale of 0-10, 702 respondents (75.2%) felt that the explanations of the test result were easy to understand (7 or higher). Ninety-one patients (9.8%) started their recommended treatment. Many patients could not receive recommended treatment because no approved drugs or clinical trials were available (102/177, 57.6%). Ninety-eight patients (10.5%) did not wish their findings to be disclosed. Overall satisfaction with the CGP test process was high, with 602 respondents (64.5%) giving a score of 7-10. The major reason for choosing 0-6 was that the CGP test result did not lead to new treatment (217/277, 78.3%). In conclusion, satisfaction with the CGP test process was high. Patients and family members need better access to information. More patients need to be treated with genomically matched therapy.

DOI： 10.1111/cas.16065

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

DOI： 10.1186/s12903-023-03586-8

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本歯周病学会  

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記述言語：日本語   出版者・発行元：(公社)日本臨床細胞学会  

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記述言語：日本語   出版者・発行元：(NPO)日本歯周病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

With the rapid expansion of genomic medicine, more citizens are compelled to think about genetics in their daily lives. This study aims to explore appropriate types of educational media and methods to enlighten activities for genetics and hereditary cancer. We presented an 18-min YouTube video on genetics and hereditary cancer to participants at a scientific event, Science Agora 2020, and administered a web questionnaire to investigate their opinions about when and how citizens should start learning about genetics and hereditary cancer. We recruited 133 participants who watched the video, and 26.3% (35/133) responded to the questionnaire. Most of them were evaluated to understand and appreciate the contents of the video. They identified websites, or videos as suitable learning media, irrespective of their sex, age, or profession. They highlighted upper elementary school or junior high school as appropriate educational stages to start learning about genetics and hereditary cancer to facilitate collecting their own genetic information by themselves. Our findings show that educational institutions should provide opportunities to learn about genetics and hereditary cancers, especially for upper elementary school and junior high school students, using learning media, such as videos, depending on their level or demand.

DOI： 10.1007/s12687-023-00663-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Few studies have been conducted on comprehensive genomic profiling (CGP) panels in Japanese patients with thoracic malignancies after completing standard treatment. Consequently, its value in clinical practice remains unclear. METHODS: We conducted a retrospective study of Japanese patients with thoracic malignancies who underwent CGP between June 2019 and November 2022 at our hospital. We evaluated the detection rate of actionable genetic alterations and percentage of patients who received genomically-matched therapy. Furthermore, we examined the value of the CGP panel in patients who underwent multiplex gene-panel testing prior to their initial treatment. This study was performed in accordance with the principles of the Declaration of Helsinki. RESULTS: The study included 56 patients, of whom 47 (83.9%) had actionable genetic alterations and 8 (14.3%) received genomically-matched therapy. Of these, four patients were treated with approved drugs and three patients were treated with investigational agents. In addition, one patient was treated with approved drugs using the patient-directed care system. Of the 17 patients who had multiplex gene-panel testing performed at the start of their initial therapy, two (11.8%) were newly identified by the CGP panel and subsequently received genomically-matched therapy. EGFR L718Q and MET amplification were observed in two of the seven patients with epidermal growth factor receptor-tyrosine kinase inhibitor resistance. CONCLUSIONS: The CGP panel could identify genetic alterations, thereby facilitating genomically-matched therapy, even in patients with thoracic malignancies who could not be identified using multiplex gene-panel testing.

DOI： 10.1016/j.resinv.2023.08.005

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記述言語：英語  

DOI： 10.1111/pin.13377

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. The accumulated evidence of tumor agnostic agent has been made since PD-1 inhibitor was approved and used in clinical practice. Therefore, we have revised the guideline "Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition". METHODS: Clinical questions regarding medical care were formulated for patients with dMMR advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO and the public comments among all societies' members were done. RESULTS: The current guideline describes two clinical questions and eight recommendations for whom, when, and how MMR status should be tested. CONCLUSION: In this guideline, the committee proposed eight recommendations for performing MMR testing properly to select patients who are likely to benefit from immunotherapy.

DOI： 10.1007/s10147-023-02397-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The development of novel antitumor agents and accompanying biomarkers has improved survival across several tumor types. Previously, we developed recommendations for tumor-agnostic treatments in patients with solid tumors with DNA mismatch repair deficient or neurotrophic receptor tyrosine kinase fusions. Recently, immune checkpoint inhibitors have shown efficacy in patient with tumor mutation burden-high (TMB-H) solid tumors and have been established as a third tumor-agnostic agent, making it necessary to develop the guideline prioritized for these patients. Clinical questions regarding medical care were formulated for patients with TMB-H advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. The current guideline describes three clinical questions and seven recommendations for whom, when, and how TMB should be tested, and what is recommended for patients with TMB-H advanced solid tumors. In this guideline, the committee proposed seven recommendations for performing TMB testing properly to select patients who are likely to benefit from immunotherapy.

DOI： 10.1007/s10147-023-02360-8

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report a case of rare and aggressive ovarian carcinosarcoma with a germline pathogenic BRCA2 variant. A patient with a history of breast cancer who developed an inflammatory ovarian tumor with peritonitis carcinomatosis involving the appendix suffered from cachexia. Following three cycles of weekly paclitaxel and carboplatin chemotherapy, emergency surgery was required owing to sepsis. Bilateral salpingo-oophorectomy, total hysterectomy, appendectomy, and small intestine adhesiolysis were performed. Histologically, the tumor comprised an admixture of carcinomatous and sarcomatous components, with involvement of the appendix, which had caused perforation and abscess formation. The final diagnosis was ovarian carcinosarcoma with a germline pathogenic BRCA2 variant, c.658_659del (p.Val220fs). The patient responded completely to adjuvant chemotherapy. A combination of chemotherapy and surgery might be beneficial to patients with ovarian carcinosarcoma and germline pathogenic BRCA2 variants with a poor general condition. This is the first report of ovarian carcinosarcoma with a germline pathogenic BRCA2 variant that responded favorably to chemotherapy.

DOI： 10.1111/jog.15736

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Clinical trials have reported the efficacy of tropomyosin receptor kinase (TRK) inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors. The accumulated evidence of tumor-agnostic agent has made since TRK inhibitors were approved and used in clinical practice. Therefore, we have revised the 'Japan Society of Clinical Oncology (JSCO)/Japanese Society of Medical Oncology (JSMO)-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese Society of Pediatric Hematology/Oncology (JSPHO)'. METHODS: Clinical questions regarding medical care were formulated for patients with NTRK fusion-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by JSCO, JSMO, and JSPHO voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. RESULTS: The current guideline describes 3 clinical questions and 14 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. CONCLUSION: The committee proposed 14 recommendations for performing NTRK testing properly to select patients who are likely to benefit from TRK inhibitors.

DOI： 10.1007/s10147-023-02345-7

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担当区分：筆頭著者   記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本遺伝カウンセリング学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Comprehensive genomic profiling (CGP) tests have been nationally reimbursed in Japan since June 2019 under strict restrictions, and over 46,000 patients have taken the test. Core Hospitals and Designated Hospitals host molecular tumor boards, which is more time-consuming than simply participating in them. We sent a questionnaire to government-designated Cancer Genomic Medicine Hospitals, including all 12 Core Hospitals, all 33 Designated Hospitals, and 117 of 188 Cooperative Hospitals. The questionnaire asked how much time physicians and nonphysicians spent on administrative work for cancer genomic medicine. For every CGP test, 7.6 h of administrative work was needed. Physicians spent 2.7 h/patient, while nonphysicians spent 4.9 h/patient. Time spent preparing for molecular tumor boards, called Expert Panels, was the longest, followed by time spent participating in Expert Panels. Assuming an hourly wage of \24,000/h for physicians and \2800/h for nonphysicians, mean labor cost was \78,071/patient. On a monthly basis, more time was spent on administrative work at Core Hospitals compared with Designated Hospitals and Cooperative Hospitals (385 vs. 166 vs. 51 h/month, respectively, p < 0.001). Consequently, labor cost per month was higher at Core Hospitals than at Designated Hospitals and Cooperative Hospitals (\3,951,854 vs. \1,687,167 vs. \487,279/month, respectively, p < 0.001). Completing a CGP test for a cancer patient in Japan is associated with significant labor at each hospital, especially at Core Hospitals. Streamlining the exchange of information and simplifying Expert Panels will likely alleviate this burden.

DOI： 10.1111/cas.15833

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記述言語：日本語   出版者・発行元：(公社)日本臨床細胞学会  

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記述言語：日本語   出版者・発行元：(公社)日本臨床細胞学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The acquisition of high-quality biospecimens and the appropriate handling of these materials are indispensable for successful clinical sequencing. We developed a cancer clinical sequencing system targeting 160 cancer genes: PleSSision-Rapid. Through the PleSSision-Rapid system, we have analyzed DNA quality evaluated by DIN (DNA integrity number) with 1329 formalin-fixed paraffin embedded (FFPE) samples including 477 prospectively collected tissues for genomic test (P) and 852 archival samples after routine pathological diagnosis (A1/A2). As a result, the samples with more than DIN 2.1 was 92.0% (439/477) in prospectively collected sample (P), while it was 85.6% (332/388) and 76.7% (356/464) in two types of archival samples (A1/A2). We performed the PleSSision-Rapid sequence using the samples with over DIN 2.1 and DNA concentration >10 ng/μL with which we were able to construct a DNA library, and the probability of sequence success was almost equivalent during all types of specimen processing, at 90.7% (398/439) in (P), 92.5% (307/332) in (A1) and 90.2% (321/356) in (A2), respectively. Our result indicated the clinical benefit to prepare the prospective collection of FFPE materials for indisputable clinical sequence, and that DIN ≥ 2.1 would be a solid parameter for sample preparation of comprehensive genomic profiling tests.

DOI： 10.1111/pin.13318

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

DOI： 10.1002/cncr.34582

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Many efforts are underway to develop novel therapies against the aggressive high-grade serous ovarian cancers (HGSOCs), while our understanding of treatment options for low-grade (LGSOC) or mucinous (MUCOC) of ovarian malignancies is not developing as well. We describe here a functional precision oncology (fPO) strategy in epithelial ovarian cancers (EOC), which involves high-throughput drug testing of patient-derived ovarian cancer cells (PDCs) with a library of 526 oncology drugs, combined with genomic and transcriptomic profiling. HGSOC, LGSOC and MUCOC PDCs had statistically different overall drug response profiles, with LGSOCs responding better to targeted inhibitors than HGSOCs. We identified several subtype-specific drug responses, such as LGSOC PDCs showing high sensitivity to MDM2, ERBB2/EGFR inhibitors, MUCOC PDCs to MEK inhibitors, whereas HGSOCs showed strongest effects with CHK1 inhibitors and SMAC mimetics. We also explored several drug combinations and found that the dual inhibition of MEK and SHP2 was synergistic in MAPK-driven EOCs. We describe a clinical case study, where real-time fPO analysis of samples from a patient with metastatic, chemorefractory LGSOC with a CLU-NRG1 fusion guided clinical therapy selection. fPO-tailored therapy with afatinib, followed by trastuzumab and pertuzumab, successfully reduced tumour burden and blocked disease progression over a five-year period. In summary, fPO is a powerful approach for the identification of systematic drug response differences across EOC subtypes, as well as to highlight patient-specific drug regimens that could help to optimise therapies to individual patients in the future.

DOI： 10.1038/s41416-022-02067-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Patients found to have presumed germline pathogenic variants (PGPVs) during comprehensive genomic profiling (CGP) require genetic counseling (GC) referrals. We retrospectively investigated the outcomes of patients with PGPVs. Among 159 patients who underwent CGP, we recommended GC for the 16 patients with PGPVs (3 with [FG group] and 13 without [G Group] a family/personal history of hereditary cancer) as well as for the 8 patients with no PGPVs, but a history (F group); 2 (67%), 5 (38%), and 3 (38%) patients received GC in the FG, G, and F groups, respectively. Germline testing results were positive in 1 and 2 patients of the FG and G groups, respectively. Among the patients recommended for GC, 58% did not receive GC due to lack of interest, poor performance status, or death. CGP contributes to the identification of germline variants in patients without a history of hereditary cancer. However, the proportion of patients who undergo GC should be improved.

DOI： 10.18926/AMO/64117

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

J-GLOBAL

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PubMed

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

J-GLOBAL

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

About 4 and a half years have passed since"Cancer Genome Medicine"was first mentioned in the Third Phase of the Basic Plan to Promote Cancer Control Programs that started in October 2017. Currently, cancer genomic medicine is being carried out by the cancer gene panel test, which is covered by public insurance, mainly at the 12 Cancer Genome Medicine Core Center Hospital designated nationwide by the Ministry of Health, Labor, and Welfare in Japan. Cancer genomic medicine has come to be positioned as a standard medical treatment. However, there are various challenges in operating an expert panel that professionally examines the results of the gene panel tests and reports treatment recommendations and secondary findings that suggest hereditary tumors. In addition, there is an urgent need to disseminate and educate healthcare professionals and patients about cancer genomic medicine. In this panel discussion on January 14, 2022, 10 panelists discussed how to solve these issues and the prospects for the future.

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

J-GLOBAL

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記述言語：英語  

A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient's daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance.

DOI： 10.18926/AMO/63908

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cognitive function progressively declines with advancing age. The aging process can be promoted by obesity and attenuated by exercise. Both conditions affect levels of the chemokine CX3CL1 in peripheral tissues; however, its role in cognitive aging is unknown. In the current study, we administered CX3CL1 into the peritoneal cavity of aged mice to investigate its impact on the aging process. In the peritoneal cavity, CX3CL1 not only reversed the age-associated accumulation of cells expressing the senescence marker p16INK4a but also increased peritoneal phagocytic activity, indicating that CX3CL1 affected the phenotypes of peritoneal cells. In the hippocampus of aged mice, intraperitoneal administration of CX3CL1 increased the number of Type-2 neural stem cells and promoted brain-derived neurotrophic factor (BDNF) expression. This treatment, furthermore, improved novel object recognition memory impaired with advancing age. Intraperitoneal transplantation of peritoneal cells from CX3CL1-treated aged mice improved novel object recognition memory in recipient aged mice. It indicates that peritoneal cells have a critical role in the CX3CL1-induced improvement of recognition memory in aged mice. Vagotomy inhibited the CX3CL1-induced increase in BDNF expression, demonstrating that the vagus nerve is involved in the hippocampal BDNF expression induced by intraperitoneal administration of CX3CL1. Thus, our results demonstrate that a novel connection among the peritoneal cells, the vagus nerve, and the hippocampus can reverse the age-associated decline in recognition memory.

DOI： 10.1007/s11357-022-00579-3

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記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(有)科学評論社  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本遺伝カウンセリング学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本遺伝カウンセリング学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本遺伝カウンセリング学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In June 2019, the Japanese National Health Insurance (NHI) system introduced coverage for two types of tumor genomic profiling (TGP): FoundationOneⓇ CDx (F1) and OncoGuide™ NCC OncoPanel System (NCCOP). TGP sometimes reveals germline variants that are potentially pathogenic as secondary findings (SFs). We conducted a questionnaire-based survey to find out the operational statuses of F1 and NCCOP at institutions where TGP was performed to elucidate issues related to SFs. Responses were received from 97 of 112 institutions (86.6%). As of May 31, 2020, 88 (90.7%) and 78 (80.4%) institutions started performing F1 and NCCOP, respectively. Since F1 only examines tumor samples, germline confirmatory testing is necessary to determine whether they are actually germline pathogenic variants (GPVs). When physicians are obtaining informed consent all but 2.3% of the patients requested SF disclosure. Conversely, when presumed germline pathogenic variants (PGPVs) were detected, 46.2% were not willing to receive confirmatory tests as they wanted to prioritize cancer treatment over SFs investigation, while only 23.3% underwent confirmatory tests. Problems in cancer genomic medicine reported by clinical genetics departments included short-staffing (n = 10), insufficient interdepartmental cooperation (n = 9), inconsistent understanding of genetics among healthcare professionals (n = 8), and low utilization rate of SFs due to lack of insurance coverage for confirmatory tests and post-test health checkups (n = 8). Solutions include; determining the appropriate timing to confirm patient intent on SF disclosure, covering confirmatory tests for PGPVs by the NHI, and establishing cooperation between the oncology and clinical genetics departments.

DOI： 10.1038/s10038-022-01028-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer. METHODS: We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease. RESULTS: TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer. CONCLUSION: The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.

DOI： 10.3802/jgo.2022.33.e50

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記述言語：英語  

DOI： 10.1016/j.amjmed.2022.02.042

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記述言語：日本語   出版者・発行元：(公社)日本整形外科学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Gynecologic cancers are more often caused by genetic factors than other cancers. Genetic testing has become a promising avenue for the prevention, prognosis, and treatment of cancers. This review describes molecular features of gynecologic tumors linked to hereditary syndromes, gives an overview of the current state of clinical management, and clarifies the role of gynecology in the treatment of hereditary tumors. Typical hereditary gynecologic tumors include hereditary breast and ovarian cancer, Lynch syndrome, Peutz-Jeghers syndrome, and Cowden syndrome. Multigene panel testing, which analyzes a preselected subset of genes for genetic variants, has recently become the first-choice test because it can provide more accurate risk assessment than a single test. Furthermore, comprehensive genomic cancer profiling enables personalized cancer treatment and aids in germline findings.

DOI： 10.1111/jog.15197

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ataxia-telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.

DOI： 10.3390/ijms23010523

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Homologous recombination (HR) is a vital process for repairing DNA double-strand breaks. Germline variants in the HR pathway, comprising at least 10 genes, such as BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK2, NBS1(NBN), PALB2, RAD51C, and RAD51D, lead to inherited susceptibility to specific types of cancers, including those of the breast, ovaries, prostate, and pancreas. The penetrance of germline pathogenic variants of each gene varies, whereas all their associated protein products are indispensable for maintaining a high-fidelity DNA repair system by HR. The present review summarizes the basic molecular mechanisms and components that collectively play a role in maintaining genomic integrity against DNA double-strand damage and their clinical implications on each type of hereditary tumor.

DOI： 10.3390/ijms23010348

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BioMed Central Ltd  

DOI： 10.1186/s13053-020-00160-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development. CASE PRESENTATION: A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3'-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma. CONCLUSIONS: We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.

DOI： 10.1186/s13053-021-00205-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.

DOI： 10.1007/s00428-021-03232-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This study aimed to investigate the clinical benefit of dose-dense paclitaxel plus carboplatin (TC) with bevacizumab therapy for advanced ovarian, fallopian tube, and primary peritoneal cancer patients in the neoadjuvant setting. METHODS: Ovarian, fallopian tube or primary peritoneal cancer patients with stage III-IV disease received neoadjuvant chemotherapy (NAC) every 3 weeks consisting of paclitaxel (80 mg/m2) on days 1, 8, and 15; carboplatin (AUC 6.0 mg/mL × min.) on day 1; and bevacizumab (15 mg/kg) on day 1. Interval debulking surgery (IDS) was performed after 3 cycles of dose-dense TC-bevacizumab therapy. The primary endpoint was the rate of complete resection by IDS. Secondary endpoints were treatment completion rate, treatment exposure, response rate to NAC, adverse events, and perioperative complications. RESULTS: Twenty-four patients were included in this study. The median age was 55.5 years (37-80 years), and most patients had high-grade serous carcinoma accounted (n = 18). IDS was performed in all patients with complete resection achieved in 75% (95% confidence interval: 57.7-92.3%). The lower limit exceeded the preset threshold rate of 55%. The response rate to NAC was 79%, and serum CA125 levels were in the normal range after NAC in 57% of patients. Grade 4 hematological toxicities and grade 3/4 non-hematological toxicities occurred in 29% and 17% of patients during NAC, respectively. Grade 3/4 perioperative complications were seen in 29% of patients, but no gastrointestinal perforations or treatment-related deaths occurred. CONCLUSIONS: Neoadjuvant dose-dense TC-bevacizumab therapy was well tolerated, and a satisfactory rate of complete resection by IDS was achieved.

DOI： 10.1007/s10147-021-02050-3

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記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Long-chain triglycerides (LCTs) intake strongly stimulates GIP secretion from enteroendocrine K cells and induces obesity and insulin resistance partly due to GIP hypersecretion. In this study, we found that medium-chain triglycerides (MCTs) inhibit GIP secretion after single LCT ingestion and clarified the mechanism underlying MCT-induced inhibition of GIP secretion. MCTs reduced the CCK effect after single LCT ingestion in wild-type (WT) mice, and a CCK agonist completely reversed MCT-induced inhibition of GIP secretion. In vitro studies showed that medium-chain fatty acids (MCFAs) inhibit long-chain fatty acid (LCFA)-stimulated CCK secretion and increase in intracellular Ca2+ concentrations through inhibition of GPR120 signaling. Long-term administration of MCTs reduced obesity and insulin resistance in high-LCT diet-fed WT mice, but not in high-LCT diet-fed GIP-knockout mice. Thus, MCT-induced inhibition of GIP hypersecretion reduces obesity and insulin resistance under high-LCT diet feeding condition.

DOI： 10.1016/j.isci.2021.102963

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pancreatic cancer is associated with both family and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected the germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/PRSS1 as high-risk genes. A latest genome-wide association study revealed the common, but low-risk germline variants in pancreatic cancer patients. Active pancreatic surveillance using magnetic resonance imaging and endoscopic ultrasound is recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these germline pathogenic variants to improve the detection rate and prognosis of pancreatic cancer. Since poly-ADP-ribose polymerase (PARP) inhibitor has been shown to be effective in improving the prognosis of BRCA-positive pancreatic cancer as well as hereditary breast and ovarian cancer syndrome, PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring the BRCA1/2 germline variant. This review highlights the importance of surveillance for germline pathogenic variants in pancreatic cancer and is expected to lead to improvements in the diagnosis and prevention of pancreatic cancer as well as facilitate the development of effective therapeutic strategies and precision medicine.

DOI： 10.1007/s10147-021-02015-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

[Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients.[Methods] Sixty-five patients aged 40 years or younger, who were diagnosed with endometrial cancer, were enrolled in this study. Targeted sequencing of a hereditary colorectal cancer-related gene panel including the MMR genes MLH1, MSH2, MSH6, and PMS2 was conducted on DNA samples extracted from blood cells.[Results] Overall, 6 missense variants (2 in MSH2, 2 in MSH6, and 2 in PMS2), 1 inframe deletion variant in MSH2, 1 splice variant in MSH2, and 1 two-base substitution in the 3' untranslated region in MLH1 were detected in 9 (13.8%) patients. Among these, the splice variant c.1276G > T (p.Ile411_Gly426del16) in MSH2 was annotated as pathogenic, while other variants were of uncertain significance. The patient with the pathogenic variant had a family history of endometrial and colorectal cancer and was diagnosed with endometrial cancer at age 35.[Conclusion] The incidence of LS among Japanese endometrial cancer patients of reproductive age (≤ 40 years) in this study was at least 1.5%; however, 12.3% of patients had variants of uncertain significance in MMR genes.

DOI： 10.1007/s10147-021-01953-5

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記述言語：英語  

Secretory carcinoma of the skin is an extremely rare adnexal tumor, histopathologically identical to homologous lesions in the salivary glands and breast tissue. Although this tumor was previously reported as indolent, we report a case of secretory carcinoma of the skin with metastases and recurrence. The patient, a 31-year-old women, had a subcutaneous mass in the right axilla. The resected specimen contained a circumscribed mass, with proliferating tumor cells that exhibited prominent nucleoli. They exhibited glandular and papillary growth patterns and there were amphophilic secretions in the glands. Immunohistochemically, the tumor cells were positive for mammaglobin and S100. The tumor was surrounded by sweat glands and there was no mammary glandular tissue, suggesting that it was derived from axillary sweat glands. Accordingly, we made a diagnosis of secretory carcinoma of the skin. Four years after the operation, there were metastases in both lungs. The resected specimen revealed a tumor identical to that of the original skin tumor. Next-generation sequencing-based multiplex gene assay performed on the metastatic tissue revealed an ETV6-NTRK3 fusion gene. This is a rare case report of secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs.

DOI： 10.1111/cup.14028

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hereditary colorectal cancer (HCRC) accounts for < 5% of all colorectal cancer cases. Some of the unique characteristics commonly encountered in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics necessitate different management approaches, including diagnosis, treatment or surveillance, from sporadic colorectal cancer management. There are two representative HCRC, named familial adenomatous polyposis and Lynch syndrome. Other than these two HCRC syndromes, related disorders have also been reported. Several guidelines for hereditary disorders have already been published worldwide. In Japan, the first guideline for HCRC was prepared by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), published in 2012 and revised in 2016. This revised version of the guideline was immediately translated into English and published in 2017. Since then, several new findings and novel disease concepts related to HCRC have been discovered. The currently diagnosed HCRC rate in daily clinical practice is relatively low; however, this is predicted to increase in the era of cancer genomic medicine, with the advancement of cancer multi-gene panel testing or whole genome testing, among others. Under these circumstances, the JSCCR guidelines 2020 for HCRC were prepared by consensus among members of the JSCCR HCRC Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR guidelines 2020 for HCRC.

DOI： 10.1007/s10147-021-01881-4

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記述言語：英語  

Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient's family was advised to undergo genetic counseling to consider additional RCC screening.

DOI： 10.3390/ijms22157962

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記述言語：英語  

DOI： 10.1038/s41440-021-00633-1

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01160&link_issn=&doc_id=20210811280023&doc_link_id=10.1507%2Fendocrine.97.S.Update_71&url=https%3A%2F%2Fdoi.org%2F10.1507%2Fendocrine.97.S.Update_71&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND Juvenile polyposis syndrome is an uncommon, autosomal-dominant hereditary disease that is distinguished by multiple polyps in the stomach or intestinal tract. It is associated with a high risk of malignancy. Pathogenic variants in SMAD4 or BMPR1A account for 40% of all cases. CASE REPORT A 49-year-old woman underwent esophagogastroduodenoscopy because of exacerbation of anemia. She had numerous erythematous polyps in most parts of her stomach. Based on biopsy findings, juvenile polyposis syndrome (JPS) was suspected morphologically, but there was no evidence of malignancy. Colonoscopy showed stemmed hyperplastic polyps and an adenoma; video capsule endoscopy revealed no lesions in the small intestine. After preoperative surveillance, laparoscopic total gastrectomy with D1 lymph node dissection was performed to prevent malignant transformation. The pathological diagnosis was juvenile polyp-like polyposis with adenocarcinoma. In addition, a germline pathogenic variant in the SMAD4 gene was detected with genetic testing. CONCLUSIONS JPS can be diagnosed with endoscopy and genetic testing. Further, appropriate surgical management may prevent cancer-related death in patients with this condition.

DOI： 10.12659/AJCR.932241

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recently, two cancer genomic profiling tests have been approved in Japan and implemented in routine clinical practice: the FDA-approved FoundationOne CDx test, and the OncoGuide NCC Oncopanel test. The quality and quantity of DNA significantly affects the sequencing results; therefore, preparing a sufficient amount of high-quality DNA for clinical cancer genomic profiling tests is important. We examined the best practices for the extraction of cancer genomic DNA from formalin-fixed paraffin-embedded (FFPE) tumor tissues of pancreatic, lung and colon cancer specimens. We found that the quality of cancer genomic DNA extracted from 10-μm-thick FFPE samples improved significantly, compared with that from 4-μm-thick FFPE samples, suggesting that 10-μm-thick FFPE samples are preferable for clinical cancer genomic profiling tests. For convenience, we created a quick reference table for calculating the required number of FFPE slides.

DOI： 10.1111/pin.13086

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記述言語：日本語   出版者・発行元：西日本泌尿器科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13691-020-00449-9

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その他リンク： http://link.springer.com/article/10.1007/s13691-020-00449-9/fulltext.html

担当区分：責任著者   記述言語：日本語   出版者・発行元：(株)診断と治療社  

J-GLOBAL

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00525&link_issn=&doc_id=20201221170010&doc_link_id=%2Fae4sanke%2F2021%2F008801%2F011%2F0065-0072%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2021%2F008801%2F011%2F0065-0072%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hereditary gynecological cancers are caused by several inherited genes. Tumors that arise in the female reproductive system, such as ovaries and the uterus, overlap with hereditary cancers. Several hereditary cancer-related genes are important because they might lead to therapeutic targets. Treatment of hereditary cancers should be updated in line with the advent of various new methods of evaluation. Next-generation sequencing has led to rapid, economical genetic analyses that have prompted a concomitant and significant paradigm shift with respect to hereditary cancers. Molecular tumor profiling is an epochal method for determining therapeutic targets. Clinical treatment strategies are now being designed based on biomarkers based on tumor profiling. Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines significantly changed the genetic testing process in 2020 to initially consider multi-gene panel (MGP) evaluation. Here, we reviewed the molecular features and clinical management of hereditary gynecological malignancies, such as hereditary breast and ovarian cancer (HBOC), and Lynch, Li-Fraumeni, Cowden, and Peutz-Jeghers syndromes. We also reviewed cancer-susceptible genes revealed by MGP tests.

DOI： 10.3390/ijms21249504

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s10038-020-0802-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Risk-reducing salpingo-oophorectomy is performed for the primary prevention of ovarian cancer in patients with hereditary breast-ovarian cancer syndrome. We performed risk-reducing salpingo-oophorectomy for the first time in Japan in 2008, and we experienced 20 cases of risk-reducing salpingo-oophorectomy through 2019. In the past, the use of risk-reducing salpingo-oophorectomy in Japan was restricted because it was not covered by a Japanese National Health Insurance. Since April 2020, risk-reducing salpingo-oophorectomy has been covered by insurance for patients with breast-ovarian cancer syndrome and pre-existing breast cancer, and this surgery is expected to become more widely implemented in Japan. METHODS: To contribute to the widespread use of risk-reducing salpingo-oophorectomy in the future, we retrospectively reviewed 20 cases of risk-reducing salpingo-oophorectomy at our hospital cohort study to clarify the issues in its implementation. RESULTS: The variant genes for which risk-reducing salpingo-oophorectomy was indicated were BRCA1 and BRCA2 in 13 (65%) and 7 patients (35%), respectively. The median age at which risk-reducing salpingo-oophorectomy was performed was 49 years (range, 38-58), 13 patients (65%) had gone through menopause, and 16 patients (80%) had a history of breast cancer. Of the five patients (25%) with vasomotor symptoms, four received Chinese medicine, and only one received hormone replacement therapy. Occult cancer was detected in the removed ovaries in two patients (10%), although no postoperative peritoneal carcinogenesis has been observed to date. CONCLUSIONS: Women who paid for risk-reducing salpingo-oophorectomy out of pocket were older than the recommended age at which the procedure should be performed, and this may explain the higher rate of occult cancers than previously reported. We need to perform risk-reducing salpingo-oophorectomy at the recommended age to ensure that the procedure is effective for primary prevention.

DOI： 10.1093/jjco/hyaa173

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The use of primary patient-derived organoids for drug sensitivity and resistance testing could play an important role in precision cancer medicine. We developed expandable ovarian cancer organoids in < 3 weeks; these organoids captured the characteristics of histological cancer subtypes and replicated the mutational landscape of the primary tumours. Seven pairs of organoids (3 high-grade serous, 1 clear cell, 3 endometrioid) and original tumours shared 59.5% (36.1-73.1%) of the variants identified. Copy number variations were also similar among organoids and primary tumours. The organoid that harboured the BRCA1 pathogenic variant (p.L63*) showed a higher sensitivity to PARP inhibitor, olaparib, as well as to platinum drugs compared to the other organoids, whereas an organoid derived from clear cell ovarian cancer was resistant to conventional drugs for ovarian cancer, namely platinum drugs, paclitaxel, and olaparib. The overall success rate of primary organoid culture, including those of various histological subtypes, was 80% (28/35). Our data show that patient-derived organoids are suitable physiological ex vivo cancer models that can be used to screen effective personalised ovarian cancer drugs.

DOI： 10.1038/s41598-020-69488-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The development of novel antitumor agents and accompanying biomarkers has improved survival across several tumor types. Previously, we published provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors. Recently, efficacy of tropomyosin receptor kinase inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors have been established as the second tumor-agnostic treatment, making it necessary to develop the guideline prioritized for these patients. METHODS: Clinical questions regarding medical care were formulated for patients with NTRK-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO) and Japanese Society of Medical Oncology (JSMO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and Japanese Society of Pediatric Hematology/Oncology, and the public comments among all Societies' members was done. RESULTS: The current guideline describes 3 clinical questions and 15 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. CONCLUSION: In the NTRK guideline, the committee proposed 15 recommendations for performing NTRK testing properly to select patients who are likely to benefit from tropomyosin receptor kinase inhibitors.

DOI： 10.1007/s10147-019-01610-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Novel therapeutic agents have improved survival outcomes in patients with advanced solid tumors. In parallel, the development of predictive biomarkers to identify patients who are likely to benefit from a certain treatment has also contributed to the improvement of survival. Recently, clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. In Japan, a PD-1 inhibitor for dMMR advanced solid tumors, regardless of the primary tumor site, has been approved. However, there are some issues related to administering immune checkpoint inhibitors in the clinical practice setting, making it necessary to develop the guidelines. METHODS: Clinical questions (CQs) regarding medical care were formulated for patients with dMMR advanced solid tumors, and evidence to the CQs was collected by manual search to prepare recommendations. Then, the committee members voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other factors. RESULTS: The current guideline, which we consider a provisional clinical opinion at this point, describes the 11 requirements to be considered in terms of patients for whom dMMR testing is recommended, the timing and methods of dMMR testing, and clinical care systems required to perform dMMR testing properly and to administer immune checkpoint inhibitors safely. CONCLUSION: This provisional clinical opinion proposes the requirements for performing dMMR testing properly to select patients who are likely to benefit from immune checkpoint inhibitors and administering them safely.

DOI： 10.1007/s10147-019-01498-8

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記述言語：日本語   出版者・発行元：日本家族性腫瘍学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Uterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P = 6.12 × 10-25 with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma.

DOI： 10.1038/s41598-020-58066-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Malignant peritoneal mesothelioma (MPeM) is a rare and aggressive form of malignant mesothelioma. Sufficient biological tools for studying the functional characteristics of this cancer have not been developed. Therefore, in this study, a novel human cancer cell line, KOG-1, was established from ascites fluids isolated from a 39-year-old Japanese woman with pemetrexed-resistant MPeM. Cells were dendritic or linear immediately after thawing, showed a jigsaw puzzle-like and spindle arrangement during growth, and formed monolayers without contact inhibition in two-dimensional (2D) culture. The population doubling time was 13.7 h. Karyotypic and molecular genetic analyses showed that chromosome numbers ranged from 62 to 142, with a peak of 73 with complicated copy number alterations. No germline BAP1 pathogenic variant was detected. Cells expressed various tumor markers of mesothelioma, such as calretinin, podoplanin, and Wilms tumor 1 (WT-1). Drug sensitivity and resistance testing with a set of 36 drugs using 2D and three-dimensional (3D) culture models demonstrated that KOG-1 cells showed high and low sensitivity to pemetrexed under 2D and 3D culture conditions, respectively, whereas control ovarian cancer cell lines showed low sensitivity to pemetrexed under both culture conditions. This newly established cell line will be a valuable biological resource to expand the feasibility of functional studies as well as drug testing for potential therapeutic purposes in MPeM.

DOI： 10.1007/s13577-019-00286-w

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s13053-020-00160-z

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その他リンク： http://link.springer.com/article/10.1186/s13053-020-00160-z/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear. Here, we examined the prevalence of germline variants among 568 Japanese patients with BRCA1/2-wildtype HBOC syndrome and a strong family history. Pathogenic or likely pathogenic variants were identified on 12 causal genes for 37 cases (6.5%), with recurrence for 4 SNVs/indels and 1 CNV. Comparisons with non-cancer east-Asian populations and European familial breast cancer cohorts revealed significant enrichment of PALB2, BARD1, and BLM mutations. Younger onset was associated with but not predictive of these mutations. Significant somatic loss-of-function alterations were confirmed on the wildtype alleles of genes with germline mutations, including PALB2 additional somatic truncations. This study highlights Japanese-associated germline mutations among patients with BRCA1/2 wildtype HBOC syndrome and a strong family history, and provides evidence for the medical care of this high-risk population.

DOI： 10.1038/s41523-020-0163-1

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1248/yakushi.19-00217-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Poor quality of biological samples will result in an inaccurate analysis of next-generation sequencing (NGS). Therefore, methods to accurately evaluate sample integrity are needed. Among methods for evaluating RNA quality, the RNA integrity number equivalent (RINe) is widely used, whereas the DV200, which evaluates the percentage of fragments of >200 nucleotides, is also used as a quality assessment standard. In this study, we compared the RINe and DV200 RNA quality indexes to determine the most suitable RNA index for the NGS analysis. Seventy-one RNA samples were extracted from formalin-fixed paraffin-embedded tissue samples (n = 30), fresh-frozen samples (n = 25), or cell lines (n = 16). After assessing RNA quality using the RINe and DV200, we prepared two kinds of stranded mRNA sequencing libraries. Finally, we calculated the correlation between each RNA quality index and the amount of library product (1st PCR product per input RNA). The DV200 measure showed stronger correlation with the amount of library product than the RINe (R2 = 0.8208 for the DV200 versus 0.6927 for the RINe). Receiver operating characteristic curve analyses revealed that the DV200 was the better marker for predicting efficient library production than the RINe using a threshold of >10 ng/ng for the amount of the 1st PCR product per input RNA (cutoff value for the RINe and DV200, 2.3 and 66.1%; area under the curve, 0.99 and 0.91; sensitivity, 82% and 92%; and specificity, 93% and 100%, respectively). Our results indicate that NGS libraries prepared using RNA samples with the DV200 value > 66.1% exhibit greater sensitivity and specificity than those prepared with the RINe values > 2.3. These findings suggest that the DV200 is superior to the RINe, especially for low-quality RNA, because it is a more consistent assessment of the amount of the 1st NGS library product per input.

DOI： 10.1155/2020/9349132

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記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

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記述言語：日本語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among 'transcriptional factors'. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.

DOI： 10.1093/carcin/bgz046

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記述言語：日本語   出版者・発行元：(株)文光堂  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Six years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the third revised edition was published in 2017. The 2017 Guidelines includes 10 additional clinical questions (CQ), which brings the total to 95 CQ (12 on infectious disease, 28 on oncology and benign tumors, 27 on endocrinology and infertility and 28 on healthcare for women). Currently a consensus has been reached on the Guidelines and therefore the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding recommendation level (A, B, C) is indicated.

DOI： 10.1111/jog.13831

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00060&link_issn=&doc_id=20190408030015&doc_link_id=%2Faa7ayuma%2F2019%2F026901%2F016%2F0085-0088%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2019%2F026901%2F016%2F0085-0088%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01750&link_issn=&doc_id=20190215160001&doc_link_id=issn%3D0289-5803%26volume%3D37%26issue%3D2%26spage%3D9&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0289-5803%26volume%3D37%26issue%3D2%26spage%3D9&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：金原出版(株)  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00535&link_issn=&doc_id=20190228020012&doc_link_id=10.18888%2Fsp.0000000762&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fsp.0000000762&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

DOI： 10.1007/978-981-13-1519-0_19

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記述言語：英語  

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記述言語：日本語   出版者・発行元：(一社)日本女性医学学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Synchronous endometrial and ovarian cancer (SEOC) is a rare entity among gynecological cancers, which exhibits endometrioid histology in its early stages and generally has a good prognosis. However, diagnosis is difficult and recent reports have demonstrated that most clinically diagnosed cases of SEOC have clonally related cancers, indicating metastatic cancer. The association of SEOC with Lynch syndrome is also not clearly understood. We herein present the case of a 41-year-old SEOC patient with MSH2 mutation. The endometrial cancer was an endometrioid adenocarcinoma and the ovarian cancer was mainly endometrioid, but also included a clear cell carcinoma with a borderline clear cell adenofibromatous component, indicating primary ovarian cancer. Both tumors exhibited microsatellite instability (MSI) and loss of expression of MSH2 and MSH6. The patient had a family history of colorectal and gastric cancers. Genetic analysis revealed a germline mutation in exon 6 of MSH2 (c.1042C>T, p.Gln348*) and the patient was diagnosed with Lynch syndrome. This MSH2 mutation has only been registered in one case in the InSiGHT variant databases and has not been reported in a gynecological tumor or SEOC to date. This case is a rare example of a patient with genetically diagnosed Lynch syndrome who also developed SEOC. This synchronous cancer is not common, but it may be caused by Lynch syndrome. Testing for MSI and immunohistochemistry for mismatch repair deficiency is necessary in cases with suspected SEOC.

DOI： 10.3892/mco.2018.1723

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記述言語：日本語   出版者・発行元：(公社)日本医師会  

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（研究会，シンポジウム資料等）  

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記述言語：英語   掲載種別：研究論文（研究会，シンポジウム資料等）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.18632/oncotarget.25712

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記述言語：日本語   出版者・発行元：(一社)東京産科婦人科学会  

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記述言語：日本語   出版者・発行元：金原出版(株)  

J-GLOBAL

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00535&link_issn=&doc_id=20180525020017&doc_link_id=10.18888%2Fsp.0000000437&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fsp.0000000437&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J06305&link_issn=&doc_id=20180620100003&doc_link_id=%2Fai1whitc%2F2018%2F000601%2F003%2F0015-0022%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai1whitc%2F2018%2F000601%2F003%2F0015-0022%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：産婦人科漢方研究会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3802/jgo.2018.29.e21

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記述言語：日本語   出版者・発行元：(一社)日本女性医学学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/cas.13469

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hereditary colorectal cancer accounts for less than 5% of all colorectal cancer cases. Some of the unique characteristics that are commonly encountered in cases of hereditary colorectal cancer include early age at onset, synchronous/metachronous occurrence of the cancer, and association with multiple cancers in other organs, necessitating different management from sporadic colorectal cancer. While the diagnosis of familial adenomatous polyposis might be easy because usually 100 or more adenomas that develop in the colonic mucosa are in this condition, Lynch syndrome, which is the most commonly associated disease with hereditary colorectal cancer, is often missed in daily medical practice because of its relatively poorly defined clinical characteristics. In addition, the disease concept and diagnostic criteria for Lynch syndrome, which was once called hereditary non-polyposis colorectal cancer, have changed over time with continual research, thereby possibly creating confusion in clinical practice. Under these circumstances, the JSCCR Guideline Committee has developed the "JSCCR Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (HCRC)," to allow delivery of appropriate medical care in daily practice to patients with familial adenomatous polyposis, Lynch syndrome, or other related diseases. The JSCCR Guidelines 2016 for HCRC were prepared by consensus reached among members of the JSCCR Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR Guidelines 2016 for HCRC.

DOI： 10.23922/jarc.2017-028

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To describe a snapshot of international genetic testing practices, specifically regarding the use of multigene panels, for hereditary breast/ovarian cancers. We conducted a survey through the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium, covering questions about 16 non-BRCA1/2 genes. Methods: Data were collected via in-person and paper/electronic surveys. ENIGMA members from around the world were invited to participate. Additional information was collected via country networks in the United Kingdom and in Italy. Results: Responses from 61 cancer genetics practices across 20 countries showed that 16 genes were tested by > 50% of the centers, but only six (PALB2, TP53, PTEN, CHEK2, ATM, and BRIP1) were tested regularly. US centers tested the genes most often, whereas United Kingdom and Italian centers with no direct ENIGMA affiliation at the time of the survey were the least likely to regularly test them. Most centers tested the 16 genes through multigene panels; some centers tested TP53, PTEN, and other cancer syndrome-associated genes individually. Most centers reported (likely) pathogenic variants to patients and would test family members for such variants. Gene-specific guidelines for breast and ovarian cancer risk management were limited and differed among countries, especially with regard to starting age and type of imaging and risk-reducing surgery recommendations. Conclusion: Currently, a small number of genes beyond BRCA1/2 are routinely analyzed worldwide, and management guidelines are limited and largely based on expert opinion. To attain clinical implementation of multigene panel testing through evidence-based management practices, it is paramount that clinicians (and patients) participate in international initiatives that share panel testing data, interpret sequence variants, and collect prospective data to underpin risk estimates and evaluate the outcome of risk intervention strategies.

DOI： 10.1200/PO.18.00091

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(in press)  

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

DOI： 10.18632/oncotarget.22733

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyx118

Web of Science

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記述言語：日本語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/IGC.0000000000000997

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PubMed

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J03723&link_issn=&doc_id=20170807200010&doc_link_id=%2Faq9seijd%2F2017%2F004707%2F010%2F0861-0866%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9seijd%2F2017%2F004707%2F010%2F0861-0866%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：金原出版(株)  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00535&link_issn=&doc_id=20170626230016&doc_link_id=10.18888%2FJ00535.2017268170&url=https%3A%2F%2Fdoi.org%2F10.18888%2FJ00535.2017268170&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: A patient's medical history and familial cancer history are important information for assessing the risk of hereditary cancer. We have generated a self-administered questionnaire for patients with gynecologic cancer. This pilot study analyzed the usefulness of this questionnaire and the rates of patients that meet the Society of Gynecologic Oncology criteria in ovarian cancer and endometrial cancer patients. Method: Ovarian or endometrial cancer patients were recruited for this study. After informed consent was obtained, participants completed the questionnaire. Genetic risks were assessed from the data of each patient's questionnaire by Society of Gynecologic Oncology guideline. Clinical and pathological findings were compared between the genetic risk groups. Results: A total of 105 patients were identified with ovarian cancer and 56 patients with endometrial cancer eligible for this study. According to the Society of Gynecologic Oncology guideline, of the 105 ovarian cancer patients, 25 patients (23%) had a 20-25% risk and three patients (2.9%) had a 5-10% risk of hereditary breast and ovarian cancer syndrome. A further 22 patients (21%) had a 5-10% risk of Lynch syndrome. Two patients (1.9%) met the Amsterdam criteria II. Of 56 endometrial cancer patients, 24 patients (42.9%) had a 5-10% risk of Lynch syndrome. The endometrial cancer patients with genetic risk of Lynch syndrome were younger (mean age: 47.79) at diagnosis compared to patients without a genetic risk of Lynch syndrome (mean age: 57.91). Conclusions: In this study, we were able to show that the newly designed questionnaire is a useful tool for evaluating cancer family history along with Society of Gynecologic Oncology criteria or Amsterdam criteria II. When considering the risk of Lynch syndrome for a patient with ovarian cancer, it is important to collect a second and third relative's family history.

DOI： 10.1093/jjco/hyx019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyx037

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jog.13202

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyw163

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jog.13202

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記述言語：日本語   出版者・発行元：更年期と加齢のヘルスケア学会((NPO)更年期と加齢のヘルスケア)  

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記述言語：日本語   出版者・発行元：(一社)東京産科婦人科学会  

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記述言語：日本語   出版者・発行元：(一社)日本遺伝性腫瘍学会  

DOI： 10.18976/jsft.16.2_38

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J03931&link_issn=&doc_id=20170714280003&doc_link_id=%2Fcg3kazok%2F2016%2F001602%2F003%2F0038-0043%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcg3kazok%2F2016%2F001602%2F003%2F0038-0043%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(株)診断と治療社  

J-GLOBAL

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00525&link_issn=&doc_id=20171124130011&doc_link_id=%2Fae4sanke%2F2017%2F008412%2F012%2F1468-1471%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2017%2F008412%2F012%2F1468-1471%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/nature20171

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/genes7100086

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/GME.0000000000000660

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Lippincott Williams and Wilkins  

DOI： 10.1097/GME.0000000000000660

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

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記述言語：日本語   出版者・発行元：更年期と加齢のヘルスケア学会((NPO)更年期と加齢のヘルスケア)  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12958-015-0136-7

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J00525&link_issn=&doc_id=20160108220002&doc_link_id=%2Fae4sanke%2F2016%2F008301%2F003%2F0013-0019%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2016%2F008301%2F003%2F0013-0019%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report a STK11 splicing variant comprising a 131-bp insertion that is derived from intron 1, which has previously been reported to possess potent pathogenicity. The same variant was detected in a Peutz-Jeghers syndrome patient harboring a genomic deletion in the vicinity of exon 1 of the STK11 gene, which indicated that this variant was derived from the wild-type allele. We also found the same variant in other normal subjects. This variant corresponds to the predicted transcript variant of STK11 (XM_011528209), which is derived from the genomic sequence of Chr19 (NT_011295.12). Therefore, we concluded that the splicing variant was not pathogenic.

DOI： 10.1038/hgv.2016.2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：金原出版(株)  

DOI： 10.18888/J00535.2016290595

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J00535&link_issn=&doc_id=20160704080001&doc_link_id=10.18888%2FJ00535.2016290595&url=https%3A%2F%2Fdoi.org%2F10.18888%2FJ00535.2016290595&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(公社)日本医師会  

J-GLOBAL

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(一社)日本女性医学学会  

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記述言語：日本語   出版者・発行元：(一社)東京産科婦人科学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1254/fpj.146.296

PubMed

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：(一社)日本女性医学学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/IGC.0000000000000482

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Termedia Publishing House Ltd.  

DOI： 10.5114/pm.2015.54339

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/IGC.0000000000000482

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

High expression of SQSTM1/p62 (p62) protein, which functions as a hub of oncogenic signaling pathways, has been detected in several human cancers. However, the clinicopathological and functional contribution of p62 expression is largely unknown in endometrial cancers (ECs). In this study, we assessed the expression status of p62 in primary ECs (n = 194) by immunohistochemistry and analyzed its clinical significance. Although p62 was expressed in the cytoplasm and/or nucleus in primary ECs, we observed that an expression subtype, high expression of cytoplasmic p62 but low expression of nuclear p62 (cytoplasm(High)/nucleus(Low)), significantly correlated with nonendometrioid types (P = 0.002), high grade (P < 0.001), deep myometrial invasion (P = 0.025), vascular invasion (P = 0.012), and poor prognosis (P < 0.001), and may be an independent prognostic marker of ECs (P = 0.011). Furthermore, RNA interference-mediated inhibition of p62 expression in the HEC-1A EC cell line led to the reduction of invasiveness and resistance to oxidative stress in vitro, as well as the suppression of in vivo tumor growth in an orthotopic mouse model of ECs. High expression of cytoplasmic p62 is a novel prognostic biomarker of ECs, and excess p62 expression may functionally contribute to the acquirement of malignant phenotypes in EC cells.

DOI： 10.1016/j.ajpath.2015.05.008

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記述言語：日本語   出版者・発行元：(一社)日本遺伝性腫瘍学会  

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記述言語：日本語   出版者・発行元：(一社)日本女性医学学会  

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記述言語：日本語   出版者・発行元：(一社)日本女性医学学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Risk-reducing surgery (RRS) is defined as a prophylactic approach with removal of organs at high risk of developing cancer, which is performed in cases without lesions or absence of clinically significant lesions. Hereditary gynecological cancers for which RRS is performed include hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. For HBOC, RRS in the United States (US) is recommended for women with mutations in the breast cancer susceptibility (BRCA)1 and BRCA2 genes and bilateral salpingo-oophorectomy (BSO) is generally performed. This procedure may reduce the risk of breast, ovarian, Fallopian tube and primary peritoneal cancer, although ovarian deficiency symptoms occur postoperatively. For Lynch syndrome, RRS in the US is considered for postmenopausal women or for women who do not desire to bear children and BSO and hysterectomy are usually performed. This approach may reduce the risk of endometrial and ovarian cancer, although ovarian deficiency symptoms also occur. For RRS, there are several issues that must be addressed to reduce the risk of cancer development in patients with HBOC or Lynch syndrome. To the best of our knowledge, this is the first review to discuss RRS with a focus on hereditary gynecological cancer.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/IGC.0000000000000377

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/IGC.0000000000000377

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記述言語：日本語   出版者・発行元：金原出版(株)  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyu164

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyu164

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5114/pm.2015.54339

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ajpath.2015.05.008

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

J-GLOBAL

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

J-GLOBAL

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00525&link_issn=&doc_id=20150603110007&doc_link_id=%2Fae4sanke%2F2015%2F008206%2F008%2F0639-0643%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2015%2F008206%2F008%2F0639-0643%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9-2.7%. Lynch syndrome accounts for 10-15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65-75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jog.12399

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jog.12399

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2217/FON.13.180

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2217/fon.13.180

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyt171

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyt171

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記述言語：日本語   出版者・発行元：金原出版(株)  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1267/ahc.14048

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/jhg.2013.105

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/jhg.2013.105

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/jhg.2013.105

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/ol.2013.1527

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/ol.2013.1527

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記述言語：英語  

DOI： 10.3892/ol.2013.1527

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyt125

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyt125

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1200/JCO.2012.45.3019

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記述言語：英語  

DOI： 10.1200/JCO.2012.45.3019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1200/JCO.2012.45.3019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0071480

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/onc.2012.376

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/onc.2012.376

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyt036

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyt036

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記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/PGP.0b013e3182518533

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本女性医学学会  

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記述言語：日本語   出版者・発行元：(一社)日本遺伝性腫瘍学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J03931&link_issn=&doc_id=20130830390001&doc_link_id=%2Fcg3kazok%2F2013%2F001301%2F001%2F0001-0005%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcg3kazok%2F2013%2F001301%2F001%2F0001-0005%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：金原出版(株)  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0071480

Web of Science

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1093/annonc/mds492

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/or.2012.2008

Web of Science

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/or.2012.2008

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/annonc/mds492

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2217/pme.12.71

Web of Science

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2217/PME.12.71

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2217/PME.12.71

Web of Science

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J03021&link_issn=&doc_id=20120815130024&doc_link_id=%2Fai6ostoe%2F2012%2F002003%2F025%2F0489-0491%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai6ostoe%2F2012%2F002003%2F025%2F0489-0491%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PubMed

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/gcc.21916

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/gcc.21916

Web of Science

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記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Elsevier Inc.  

DOI： 10.1016/B978-0-12-388415-2.00023-8

Scopus

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/IGC.0b013e31822c271f

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/IGC.0b013e31822c271f

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/IGC.0b013e31822c271f

Web of Science

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/ijo.2011.1131

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/ijo.2011.1131

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3892/ijo.2011.1131

Web of Science

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1158/0008-5472.CAN-11-0364

Web of Science

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1158/0008-5472.CAN-11-0364

Web of Science

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記述言語：日本語   出版者・発行元：(株)永井書店  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J00534&link_issn=&doc_id=20111007170016&doc_link_id=%2Faf2sftye%2F2011%2F010304%2F016%2F0417-0421%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faf2sftye%2F2011%2F010304%2F016%2F0417-0421%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1158/0008-5472.CAN-11-0364

Web of Science

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J00525&link_issn=&doc_id=20110825150005&doc_link_id=%2Fae4sanke%2F2011%2F007809%2F006%2F1064-1068%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2011%2F007809%2F006%2F1064-1068%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：金原出版(株)  

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記述言語：日本語   出版者・発行元：(株)南江堂  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J03022&link_issn=&doc_id=20110927270002&doc_link_id=issn%3D1342-0569%26volume%3D16%26issue%3D6%26spage%3D631&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1342-0569%26volume%3D16%26issue%3D6%26spage%3D631&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

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