Researchers from the Chinese Liver Cancer Atlas project performed deep whole-genome sequencing of hepatocellular carcinoma (HCC) tumours from 494 Chinese individuals (86.4% men and 13.6% women) who received no preoperative anti-cancer treatment. According to epidemiological data, 94.5% of the enrolled patients had hepatitis B, 2.6% had hepatitis C, 26.7% drank alcohol and 36.8% smoked.

The researchers identified 23 candidate coding drivers, of which 6 were previously undescribed (for example, FGA, HNF1A and PRDM11). They also identified 31 non-coding drivers, of which 28 were previously undescribed. FGA was also described as a candidate non-coding (3′ UTR) driver, and in vitro and in vivo experiments showed that it regulated HCC progression and metastasis. In addition, 10 candidate drivers (2 coding and 8 non-coding) demonstrated marked clonality enrichment of mutations. The researchers found 5 previously undescribed mutational signatures, including the novel single-base-substitution signature SBS_H8.