The consequence of AT-rich interacting domain 2 (ARID2) depletion in liver cancers

2015 Fiscal Year Final Research Report

• Project/Area Number: 25861221
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Furuta Mayo 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 (00647183)
• Co-Investigator(Renkei-kenkyūsha): 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) ; Fujimoto Akihiro 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, 副チームリーダー (30525853)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 肝がん / ARID2 / ゲノム変異

Outline of Final Research Achievements

In liver cancers, totally we found somatic non synonymous mutations, short insertion-deletions or structural variations around ARID2 gene in 33 cases from the WGS analysis of 245 cases, resulting in 13% of liver cancers have genomic alterations in ARID2. In addition, subgroup horboring mutations in ARID2 showed the worse prognosis indicating their importance in tumorigenesis. Since the somatic mutations in ARID2 are significantly enriched with nonsense or indel mutations, the role of ARID2 in liver cancers was thought to be tumor-suppressive. To determine the native ARID2 role in hepatocarcinogenesis, we first analyzed their activity on cell growth. Knockdown of ARID2 in ARID2-intact liver cancer cell lines promoted their growth, while overexpression suppressed their growth. These results indicate that somatic loss-of-function mutations in component of chromatin regulators such as ARID2 could lead the genome-wide gene expression or epigenomic change appeared in liver cancers.

Free Research Field

分子生物学　がんゲノム