Exome sequencing of hepatitis B virus-associated advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and exhibits a propensity to infiltrate and metastasize to adjacent and other tissues. Here, we used exomic sequencing to identify somatic mutations in ten hepatitis B virus (HBV)-positive HCC patients with portal vein tumor thromboses (PVTTs), i.e., intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations that were detected. Interestingly, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the cellular survival roles of 91 of the confirmed mutated genes. The results suggest that 7 of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity on HCC cells.