Identification of aberrant pathways by integrated analysis in stepwise hepatocarcinogenesis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24249068
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nihon University
• Principal Investigator: TAKAYAMA Tadatoshi 日本大学, 医学部, 教授 (30280944)
• Co-Investigator(Kenkyū-buntansha): MIDORIKAWA Yutaka 日本大学, 医学部, 助教 (10292905) ; TSUTSUMI Shuichi 東京大学, 先端科学技術研究センター, 特任准教授 (30345152) ; TUSJI Shingo 東京大学, 先端科学技術研究センター, 特任助教 (80431823)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肝癌多段階発癌 / 次世代シークエンス / p53 / WNT / TERT / 統合解析

Outline of Final Research Achievements

Early hepatocellular carcinoma (HCC) is histologically diagnosed as the existence of intratumoral portal tracts and develops into classical HCC. To identify sequential genomic changes in stepwise hepatocarcinogenesis, we analyzed 47 early and 105 classical HCCs using next generation sequencer. Mutations in p53/RB and WNT pathways were recurrently observed both in early and classical HCCs. Exome and RNA sequences frequently showed mutation of promoter region and increased expression of TERT. On the other hand, inactivation in SWI/SNF complexes were observed more often in classical HCC (23.8%) than early HCC (8.5%, P=0.027), and mTOR/PI3K pathway was aberrantly activated in classical HCC (8.5% vs 29.5%, P=0.003) by integrated analysis. Taken together, inactivating mutations of p53/RB and WNT signaling pathways and TERT up-regulation are the first events in hepatocarcinogenesis and aberrations of SWI/SNF complexes and mTOR/PI3K pathway may play pivotal roles in the progression of HCC.

Free Research Field

消化器外科学