Hepatocellular Carcinoma Genetic Landscape

Liver cancer is the sixth most commonly diagnosed cancer worldwide and the third leading cause of cancer death. The number of cases has also been rapidly increasing in Western countries, and globally, more than 700,000 new patients are diagnosed annually. HCC arising from hepatocytes, represents the most common histological subtype of liver cancers, accounting for approximately 70-85% of all cases. Multiple etiological factors for HCC have been identified. The most important risk factor is infection with hepatitis viruses, mainly HBV and HCV. Alcohol-induced liver damage also ranks high, especially in Western countries. Virus infection or metabolic stress results in liver damage including fatty change, hepatitis, and cirrhosis, which set premalignant conditions for HCC. Chronic inflammation, virus infection, and liver regeneration in cirrhosis have been reported to induce genetic and epigenetic damage to the host genome. Most HCCs gradually develop from these premalignant stages by the accumulation of these alterations. Accordingly, highly damaged livers are extremely susceptible to multiple tumors. The next-generation sequencing (NGS) era enabled whole-genome or exome sequencing of the cancer genome within a reasonable time frame and cost. This approach is rapidly and exhaustively identify potential key genetic events, including potential molecular therapeutic targets, in HCC. The current review summarizes the data about molecular pathogenesis and signal transduction pathways in hepatocellular carcinoma considering recent results in molecular research.