Research for hepatocarcinogenesis using iPS cells with genetic mutations and information of HBV integration

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17453
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Kawai-Kitahata Fukiko (河合) 東京医科歯科大学, 医学部附属病院, 特任助教 (00755580)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 肝細胞癌 / B型肝炎ウイルス / ヒトiPS細胞

Outline of Final Research Achievements

We investigated cancer-related genes and viral integration using next generation sequencing in HCC tissues with HBV suppression by nucleotide/nucleoside analogues.
In HBs antigen positive patients with chronic persistent HBV infection, gene mutational profile and HBV integration breakpoints were similar to those in HBs antigen positive patients with normal ALT. In patients with prior HBV infection, HBV integration were found in common cancer-related genes although a total number of HBV integration breakpoints was small compared with those in chronic persistent HBV infection. Based on these results, we also established human induced pluripotent stem cell model with HBV integration breakpoints at TERT and KMT locus.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

世界的に蔓延するB型肝炎ウイルス(HBV)感染症において、HBV制御下におけるB型肝癌の癌関連遺伝子やウイルスDNAのヒトゲノムへの挿入を調べ、さらにHBV breakpointsを再現してiPS細胞株への挿入変異を導入した。HBV制御状態により発癌過程が共通するまたは異なる可能性を示したことにより今後癌進展機構など臨床的な知見となり得る。またiPS細胞を用いた新たな応用研究分野を開発する知的・技術的基盤の確立に貢献することにつながる。