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Genomic landscape of colitis-associated cancer indicates the impact of chronic inflammation

Research Project

Project/Area Number 15K15301
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Nakagawa Hidewaki  国立研究開発法人理化学研究所, 統合生命医科学研究センター, チームリーダー (50361621)

Co-Investigator(Renkei-kenkyūsha) MATSUBARA Nakahide  兵庫医科大学, 医学部, 客員教授 (70314672)
Research Collaborator FUJITA Masashi  国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (80564749)
IKEUCHI Hiroki  兵庫医科大学, 医学部, 教授 (80319863)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywordsがんゲノム / 炎症性腸疾患 / 大腸がん / 大腸癌 / ゲノムシークエンス / がん / ゲノム / 潰瘍性大腸炎
Outline of Final Research Achievements

We obtained fresh-frozen tumor tissues from 22 colitis-associated cancer (CAC) patients and performed exome sequencing and RNA-Seq. We then selected 43 recurrently mutated genes and performed targeted sequencing on 90 archive specimens from CAC patients. The most commonly mutated gene in CAC was TP53, whose mutation was found in 66%. APC mutations were found only in 16%, which were associated with differentiated adenocarcinoma, left-sided colitis, and late onset of IBD. On the other hand, mutations of another Wnt-related gene occurred in 11% of CACs and showed significant association with IBD duration, indicating its link to chronic inflammation. CACs showed distinct genetic features from conventional CRCs, while some showed similar features. Mutated genes specific to CACs, especially ones in Wnt signaling, have an implication for stratification and treatment of CAC.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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