Faculty Profiles - HIRASAWA Akira

Papers - HIRASAWA Akira

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がんゲノムプロファイリング検査による大腸癌でのBRAF阻害薬の適応判断

山本英喜, 重安邦俊, 河内麻里子, 座間味義人, 平沢晃

日本臨床薬理学会学術総会抄録集 43回 1 - 6 2022.12

RAS/BRAF解析においてPCR-rSSO法とNGS法の併用による補完性が示された大腸癌の二例

山本英喜, 重安邦俊, 柳井広之, 井上博文, 松岡博美, 青江伯規, 東影明人, 藤井敬子, 大塚文男, 草野展周, 平沢晃

日本臨床検査医学会誌 70 ( 補冊 ) 258 - 258 2022.10

がんゲノム医療における「連携」主に患者、家族・血縁者との連携にかかる課題について全国がんプロ協議会・ゲノム医療部会報告

平沢晃

癌と化学療法 49 ( 9 ) 1000 - 1001 2022.9

Language：Japanese Publisher：(株)癌と化学療法社

医療者間の連携、医療者と患者の連携および患者と家族間の連携はがん診療全般でも必要事項ではあり、がんゲノム医療のもつ特性を考えた連携を構築することが望ましい。わが国のがんゲノム医療の定義で提唱されているとおり、がん未発症者を含むがん発症予防が可能になって初めて国民の確実ながん死低減が可能になる。(著者抄録)

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骨・軟部肉腫に対するがんゲノムプロファイリング検査から検出されるpresumed germline pathogenic variantsの意義

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1770 - S1770 2022.9

[Panel Discussion - Problems in the Cancer Genomic Medicine].

Chikashi Ishioka, Manabu Muto, Shinichi Yachida, Hidekazu Shirota, Akira Hirasawa, Kiyoshi Miyagawa, Kazuto Ashizawa, Ichiro Kinoshita, Hiroshi Nishihara, Nariaki Matsuura, Akihiro Sakurai

Gan to kagaku ryoho. Cancer & chemotherapy 49 ( 9 ) 1014 - 1017 2022.9

Language：Japanese Publishing type：Research paper (scientific journal)

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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骨・軟部腫瘍の基礎科学のトピックスクリニカルシークエンスによる肉腫のゲノム医療

中田英二, 藤原智洋, 国定俊之, 二川摩周, 遠西大輔, 久保寿夫, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1533 - S1533 2022.9

[The Cooperation with Medical Staff, Medical Staff and Patients, and Patients and Their Families in Cancer Precision Medicine].

Akira Hirasawa

Gan to kagaku ryoho. Cancer & chemotherapy 49 ( 9 ) 1000 - 1001 2022.9

Liquid Biopsy Revealed HBOC Pedigree and Led to Medical Management Among the Relatives.

Chikako Ogawa, Akira Hirasawa, Reimi Sogawa, Kayoko Hasuoka, Shuta Tomida, Mashu Futagawa, Yusaku Urakawa, Mariko Kochi, Hideki Yamamoto, Keiichiro Nakamura, Hisashi Masuyama

Acta medica Okayama 76 ( 4 ) 479 - 483 2022.8

Language：English

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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Alteration in peritoneal cells with the chemokine CX3CL1 reverses age-associated impairment of recognition memory. International journal

Yoshinori Takei, Yoko Amagase, Keiko Iida, Tomohiro Sagawa, Ai Goto, Ryuichi Kambayashi, Hiroko Izumi-Nakaseko, Akio Matsumoto, Shinichi Kawai, Atsushi Sugiyama, Tatsuyuki Takada, Akira Hirasawa

GeroScience 44 ( 4 ) 2305 - 2318 2022.8

Language：English Publishing type：Research paper (scientific journal)

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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がん遺伝子パネル検査の現状と課題がんゲノム医療overview 国民のがん死低減をめざして

平沢晃

日本婦人科腫瘍学会雑誌 40 ( 3 ) 120 - 124 2022.7

Language：Japanese Publisher：(公社)日本婦人科腫瘍学会

がんゲノム医療は「がん患者の腫瘍部および正常部のゲノム情報を用いて治療の最適化・予後予測・発症予防をおこなう医療(未発症者も対象とすることがある。またゲノム以外のマルチオミックス情報も含める)」と定義される(がんゲノム医療推進コンソーシアム懇談会報告書〜国民参加型がんゲノム医療の構築に向けて〜厚生労働省HP平成29年6月27日)。「治療の最適化」についてはがん医療へコンパニオン診断の導入から、2019年6月のがん遺伝子パネル検査の保険収載を契機に、個別化治療に到達する道筋が整備されてきている。一方でがんゲノム医療は定義にあるように「がん未発症者」を含む「がん発症予防」を含む概念である。がん発症高リスクのがん未発症者に対する介入が可能になってはじめて、国民の確実ながん死低減が可能になるといえる。婦人科診療を窓口に個々のゲノム情報に応じて未発症者も既発症者の区別なく対応していき、「治療の最適化・予後予測・発症予防」によって最終的に国民のがん死低減に寄与することが可能になる。(著者抄録)

J-GLOBAL

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Cancer precision medicine and germline findings.

植野さやか, 平沢晃

月刊糖尿病・内分泌代謝科 55 ( 1 ) 126 - 135 2022.7

Surveillance for tumorous lesions in neurofibromatosis type 1

二川摩周, 二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 山本英喜, 藤原智洋, 国定俊之, 尾崎敏文, 平沢晃, 平沢晃

日本遺伝カウンセリング学会誌 43 ( 2 ) 92 - 92 2022.6

Genetic counseling for parents who wish a prenatal diagnosis for their second child although the previous child’s chromosomal abnormality was occurred in de novo

衛藤英理子, 三苫智裕, 横畑理美, 三島桜子, 大平安希子, 桐野智江, 谷和祐, 牧尉太, 早田桂, 増山寿, 秋山倫之, 大守伊織, 十川麗美, 河内麻里子, 平沢晃

日本遺伝カウンセリング学会誌 43 ( 2 ) 95 - 95 2022.6

Development and evaluation of a teaching material to improve general literacy for cancer precision medicine

十川麗美, 十川麗美, 和田敬仁, 榎朗兆, 岩本結香子, 黒飛恵子, 金井雅史, 近藤知大, 近藤知大, 本田明夏, 山田崇弘, 平沢晃, 武藤学, 小杉眞司

日本遺伝カウンセリング学会誌 43 ( 1 ) 15 - 27 2022.5

成人になって診断のついたHajdu-Cheney症候群の一例

二川奈都子, 長谷川高誠, 西田圭一郎, 平沢晃, 河内麻里子

日本内分泌学会雑誌 98 ( 1 ) 377 - 377 2022.4

Current status and issues related to secondary findings in the first public insurance covered tumor genomic profiling in Japan: multi-site questionnaire survey. International journal

Akari Minamoto, Takahiro Yamada, Saki Shimada, Ichiro Kinoshita, Yoko Aoki, Katsutoshi Oda, Arisa Ueki, Satomi Higashigawa, Maki Morikawa, Yuki Sato, Akira Hirasawa, Masanobu Ogawa, Tomohiro Kondo, Masahiro Yoshioka, Masashi Kanai, Manabu Muto, Shinji Kosugi

Journal of human genetics 67 ( 10 ) 557 - 563 2022.3

Language：English Publishing type：Research paper (scientific journal)

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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TP53 variants in p53 signatures and the clonality of STICs in RRSO samples. International journal

Tomoko Akahane, Kenta Masuda, Akira Hirasawa, Yusuke Kobayashi, Arisa Ueki, Miho Kawaida, Kumiko Misu, Kohei Nakamura, Shimpei Nagai, Tatsuyuki Chiyoda, Wataru Yamagami, Shigenori Hayashi, Fumio Kataoka, Kouji Banno, Kokichi Sugano, Hajime Okita, Kenjiro Kosaki, Hiroshi Nishihara, Daisuke Aoki

Journal of gynecologic oncology 33 ( 4 ) e50 2022.3

Language：English Publishing type：Research paper (scientific journal)

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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Hemothorax and Bloody Ascites Caused by Vascular Ehlers-Danlos Syndrome. International journal

Shuichi Tanaka, Hiroyuki Honda, Kou Hasegawa, Koji Tomita, Reimi Sogawa, Hideki Yamamoto, Takao Hiraki, Akira Hirasawa, Fumio Otsuka

The American journal of medicine 135 ( 7 ) e210-e211 2022.3

がんゲノム中核拠点病院における、がん遺伝子パネルで同定されたGermline Findingsに対する診療システムの構築

中田英二, 二川摩周, 国定俊之, 藤原智洋, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 2 ) S439 - S439 2022.3

Hereditary gynecologic tumors and precision cancer medicine. International journal

Chikako Ogawa, Akira Hirasawa, Naoyuki Ida, Keiichiro Nakamura, Hisashi Masuyama

The journal of obstetrics and gynaecology research 48 ( 5 ) 1076 - 1090 2022.2

Language：English Publishing type：Research paper (scientific journal)

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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Papers - HIRASAWA Akira