Identification of novel fusion genes in gastric cancer by whole transcriptome sequencing: Discovery of potential therapeutic targets for gastric cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25290074
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Medical genome science
• Research Institution: National Cancer Center Japan
• Principal Investigator: Hosoda Fumie 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (30219191)
• Co-Investigator(Renkei-kenkyūsha): SHIBATA Tatsuhiro 国立研究開発法人国立がん研究センター, 研究所がんゲノミクス研究分野, 分野長 (90311414) ; TOTOKI Yasushi 国立研究開発法人国立がん研究センター, 研究所がんゲノミクス研究分野, ユニット長 (10373333) ; ARAI Yasuhito 国立研究開発法人国立がん研究センター, 研究所がんゲノミクス研究分野, 主任研究員 (80222727) ; TANIGUCHI Hirokazu 国立研究開発法人国立がん研究センター, 中央病院病理科, 医員 (30415525)
• Research Collaborator: ROKUTAN Hirofumi
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 胃癌 / トランスクリプトーム / 融合遺伝子 / 治療標的分子

Outline of Final Research Achievements

Genomic rearrangements are frequently associated with cancer and can generate gene fusions with oncogenic property. Such somatic fusion genes are good targets for cancer therapy, but remain poorly characterized in gastric cancer. To discover new therapeutic targets, we applied a whole transcriptome sequencing approach to 218 gastric tumor specimens. We have predicted 1107 chimeric transcripts by read-pair mapping analysis, including 164 recurrent in-frame fusion genes and 160 singleton with more than ten mapped sequence reads. RT-PCR analysis of the 400 candidate transcripts revealed that 230 fusion genes are expressed in a tumor-specific manner. We found four important kinase fusion genes including a RET fusion as a promising therapeutic target. The novel RET fusion gene has been shown to transform NIH3T3 cell and to form tumor in nude mice. The RET kinase inhibitor such as vandetanib and XL184, effectively inhibited transformed NIH3T3 cell proliferation.

Free Research Field

ゲノム医科学　分子腫瘍学