Genetic alterations in advanced HBV-related HCC with portal vein tumor thrombosis: Insights from next generation DNA sequencing

Roongruedee Chaiteerakij, Lewis R. Roberts

Research output: Contribution to journalComment/debate

5 Scopus citations

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, 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 roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.

Original languageEnglish (US)
Pages (from-to)1042-1044
Number of pages3
JournalJournal of hepatology
Volume58
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • HBV-related HCC
  • Hepatocellular carcinoma
  • Next generation sequencing

ASJC Scopus subject areas

  • Hepatology

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