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.

Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma