Hepatocellular carcinoma (HCC) is a global health issue and the fourth leading cause of cancer deaths worldwide. Large-scale HCC genome sequencing analyses have identified core drivers (TERT, TP53, and CTNNB1/AXIN1) as initial molecular events, and other low-frequent drivers that include therapeutically targetable ones. The recent genetic analysis uncovered a distinctive driver gene landscape in precancerous lesions, arguing a discontinuous process at early HCC development. In advanced tumors, intra-tumoral heterogeneity through clonal evolution processes is common, and it displays clear geographic segregation genetically and epigenetically. Diverse epidemiological risk factors for HCC mirrors heterogeneous mutational processes among patient cohorts with distinctive ethnicity, environmental exposures, and lifestyles. The genetic information of individual tumors has been utilized for optimizing treatments, early diagnosis, and monitoring recurrence. It will expand the opportunity for screening high-risk populations, thereby preventing hepatocarcinogenesis in the near future.

肝细胞癌 (HCC) 是一个全球性的健康问题，也是全球癌症死亡的第四大原因。大规模 HCC 基因组测序分析已确定核心驱动因素（TERT、TP53和CTNNB1/AXIN1) 作为初始分子事件，以及包括治疗靶向事件在内的其他低频驱动因素。最近的基因分析揭示了癌前病变中一个独特的驱动基因景观，认为早期 HCC 发展过程是不连续的。在晚期肿瘤中，通过克隆进化过程产生的肿瘤内异质性很常见，并且在遗传和表观遗传上显示出明显的地理隔离。HCC 的不同流行病学危险因素反映了具有独特种族、环境暴露和生活方式的患者队列中的异质突变过程。单个肿瘤的遗传信息已被用于优化治疗、早期诊断和监测复发。它将扩大筛查高危人群的机会，