Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma

Abstract

Kenneth Kinzler and colleagues report exome sequencing of ten hepatocellular carcinoma tumors and matched normal tissue. They identify inactivating mutations in the chromatin remodeling gene ARID2 in a total of 9 out of 139 HCC tumors. Through exomic sequencing of ten hepatitis C virus (HCV)-associated hepatocellular carcinomas (HCC) and subsequent evaluation of additional affected individuals, we discovered novel inactivating mutations of ARID2 in four major subtypes of HCC (HCV-associated HCC, hepatitis B virus (HBV)-associated HCC, alcohol-associated HCC and HCC with no known etiology). Notably, 18.2% of individuals with HCV-associated HCC in the United States and Europe harbored ARID2 inactivation mutations, suggesting that ARID2 is a tumor suppressor gene that is relatively commonly mutated in this tumor subtype.