Genetics of Hepatocellular Carcinoma: Risk Stratification, Clinical Outcome, and Implications for Therapy

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a highly heterogeneous disease with a dismal prognosis. During the last decade, significant efforts to elucidate the genetic background of HCC have led to the identification of the major genomic aberrations driving the disease. Nonetheless, only few of them (∼30%) are currently amenable for treatment. Two clear-cut gene expression based HCC molecular classes, namely “proliferation” and “nonproliferation,” have been described. The “proliferation” class is characterized by enrichment in poor prognostic signatures, a more aggressive phenotype, and poorer outcome. In addition, exposure-specific mutational patterns have been identified (smoking, alcohol, aflatoxin B, etc.), whereas molecular signatures from the surrounding cirrhotic liver and single nucleotide polymorphisms have been linked with HCC occurrence. Despite such advances, no molecular biomarker has yet been incorporated in clinical decision-making. In this review, the authors summarize the most recent molecular findings in HCC pointing toward prospects for translating this knowledge into specific clinical interventions.