Importance of loss-of-function of ARID family proteins in liver cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09340
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Chiba University
• Principal Investigator: Chiba Tetsuhiro 千葉大学, 大学院医学研究院, 講師 (00381583)
• Research Collaborator: IWAMA ATSUSHI ; KATO NAOYA
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: エピジェネティクス

Outline of Final Research Achievements

Epigenetic dysregulation is closely involved in cancer development and progression. ARID family proteins, including ARID1A, ARID1B, and ARID2, are core molecules of SWI/SNF complexes and function as chromatin remodeling factors.
ARID genes function as tumor suppressor in vitro assays. Genome information analyses using TCGA data revealed that 30-40% of patients with liver cancer harbors mutation of ARID genes. Survival of patients with ARID mutation is unfavorable than those without ARID mutation due to at least in part high tumor mutation burden.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

ARID遺伝子群（ARID1A, ARID1B, ARID2）はがん抑制遺伝子として機能し、その機能喪失型変異は肝癌においても、発癌、癌の進行において重要な役割を果たすものと考えられる。今回の検討では、ARID遺伝子群に変異がある場合は、ない場合に比較してtumor mutation burdenが高く、overall survivalが不良であった。特にARID1A変異はミスマッチ修復機構を妨げ、免疫チェックポイント阻害剤(ICI)の効果が高いことも報告されており、ICIの治療効果予測においても有用である可能性が示唆された。