Whole transcriptome analysis and novel therapeutic targets in biliary tract cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461040
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Arai Yasuhito 国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (80222727)
• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 胆道がん / トランスクリプトーム / 融合遺伝子 / 分子診断 / 治療標的遺伝子

Outline of Final Research Achievements

Biliary tract cancer (BTC) is an intractable cancer, with limited therapeutic options. To find out cancer driver alterations and biomarkers for personalized therapy, we performed whole transcriptome sequencing analyses of 160 BTC cases. FGFR2 fusion kinase genes we identified are one of the high-potential therapeutic targets of BTC. Novel fusion genes, ATP1B-PRKACA/PRKACB involving cAMP-dependent protein kinase (PKA) signal components (PRKACA and PRKACB) were identified in extrahepatic cholangiocarcinoma. The fusions robustly induced expression of the PRKACA and PRKACB, and demonstrated increased or comparative PKA activity compared to wild-type PKA activating downstream MAPK. These analyses pave the way to genotype-based actionable target therapy.

Free Research Field

分子腫瘍学