Genome sequencing analysis of liver cancer for precision medicine.

Liver cancer is the third leading cause of cancer-related death worldwide. Some thousands of liver cancer genome have been sequenced globally so far and most of driver genes/mutations with high frequency are established in liver cancer, including Wnt/β-catenin pathway, TP53/cell-cycle pathways, telomere maintenance, and chromatin regulators. HBV integration into cancer-related genes is also a driver event in hepatocarcinogenesis. These genes are affected by structural variants, copy-number alterations and virus integrations as well as point mutations. Etiological factors of liver cancer is most understood among common cancers, such as hepatitis, aflatoxin, alcohol, and metabolic diseases, and mutational signatures of liver cancer can provide evidence of the association between specific etiological factors and mutational signatures. Molecular classifications based on somatic mutations profiles, RNA expression profiles, and DNA methylation profiles are related with patient prognosis. For precision medicine, several actionable mutations with solid evidence such as targets of multi-kinase inhibitors is observed in liver cancer, but there is few molecular target therapy so far. It is possible that rare actionable mutations in liver cancer can guide other specific molecular therapy and immune therapy.