Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Background

Members of the neurotrophic tropomyosin receptor kinase (NTRK) gene family, NTRK1, NTRK2, and NTRK3 encode TRK receptor tyrosine kinases. Intra‐ or inter‐chromosomal gene rearrangements produce NTRK gene fusions encoding fusion proteins which are oncogenic drivers in various solid tumors.

Methods

This study investigated the prevalence of NTRK fusion genes and identified fusion partners in Japanese patients with solid tumors recorded in the Center for Cancer Genomics and Advanced Therapeutics database of comprehensive genomic profiling test.

Results

In the analysis population (n = 46,621), NTRK fusion genes were detected in 91 patients (0.20%). The rate was higher in pediatric cases (<18 years; 1.69%) than in adults (0.16%). NTRK gene fusions were identified in 21 different solid tumor types involving 38 different partner genes including 22 (57.9%) previously unreported NTRK gene fusions. The highest frequency of NTRK gene fusions was head and neck cancer (1.31%) and thyroid cancer (1.31%), followed by soft tissue sarcoma (STS; 0.91%). A total of 97 NTRK fusion gene partners were analyzed involving mainly NTRK1 (49.5%) or NTRK3 (44.2%) gene fusions. The only fusion gene detected in head and neck cancer was ETV6::NTRK3 (n = 22); in STS, ETV6::NTRK3 (n = 7) and LMNA::NTRK1 (n = 5) were common. Statistically significant mutual exclusivity of NTRK fusions with alterations was confirmed in TP53, KRAS, and APC. NTRK gene fusion was detected from 11 STS cases: seven unclassified sarcoma, three sarcoma NOS, and one Ewing sarcoma.

Conclusions

NTRK gene fusion identification in solid tumors enables accurate diagnosis and potential TRK inhibitor therapy.

DOI： 10.1002/cam4.7351

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

BACKGROUND: Paired related-homeobox 1 (PRRX1) is a transcription factor in the regulation of developmental morphogenetic processes. There is growing evidence that PRRX1 is highly expressed in certain cancers and is critically involved in human survival prognosis. However, the molecular mechanism of PRRX1 in cancer malignancy remains to be elucidated. METHODS: PRRX1 expression in human Malignant peripheral nerve sheath tumours (MPNSTs) samples was detected immunohistochemically to evaluate survival prognosis. MPNST models with PRRX1 gene knockdown or overexpression were constructed in vitro and the phenotype of MPNST cells was evaluated. Bioinformatics analysis combined with co-immunoprecipitation, mass spectrometry, RNA-seq and structural prediction were used to identify proteins interacting with PRRX1. RESULTS: High expression of PRRX1 was associated with a poor prognosis for MPNST. PRRX1 knockdown suppressed the tumorigenic potential. PRRX1 overexpressed in MPNSTs directly interacts with topoisomerase 2 A (TOP2A) to cooperatively promote epithelial-mesenchymal transition and increase expression of tumour malignancy-related gene sets including mTORC1, KRAS and SRC signalling pathways. Etoposide, a TOP2A inhibitor used in the treatment of MPNST, may exhibit one of its anticancer effects by inhibiting the PRRX1-TOP2A interaction. CONCLUSION: Targeting the PRRX1-TOP2A interaction in malignant tumours with high PRRX1 expression might provide a novel tumour-selective therapeutic strategy.

DOI： 10.1038/s41416-024-02632-8

PubMed

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.isci.2021.103342

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Language：English  

CiNii Article

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Other Link： http://t2r2.star.titech.ac.jp/cgi-bin/publicationinfo.cgi?q_publication_content_number=CTT100857867

Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

MicroRNAs are important genes in biological processes. Although the function of microRNAs has been elucidated, the relationship between the sequence and the disease is not sufficiently clear. It is important to clarify the relationship between the sequence and the disease because it is possible to clarify the meaning of the microRNA genetic code consisting of four nucleobases. Since seed theory is based on sequences, its development can be expected to reveal the meaning of microRNA sequences. However, this method has many false positives and false negatives. On the other hand, disease-related microRNA searches using network analysis are not based on sequences, so it is difficult to clarify the relationship between sequences and diseases. Therefore, RNA–RNA interactions which are caused by hydrogen bonding were focused on. As a result, it was clarified that sequences and diseases were highly correlated by calculating the electric field in microRNA which is considered as the torus. It was also suggested that four diseases with different major classifications can be distinguished. Conventionally, RNA was interpreted as a one-dimensional array of four nucleobases, but a new approach to RNA from this study can be expected to provide a new perspective on RNA-RNA interactions.

DOI： 10.3390/cells8121615

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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J-GLOBAL

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Language：English   Publisher：(一社)日本癌治療学会  

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Event date： 2024.10.28 - 2024.10.31

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2023.10.19 - 2023.10.21

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2023.4.26 - 2023.4.28

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2023.3.3 - 2023.3.4

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2022.10.13 - 2022.10.14

Language：Japanese  

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