Divergent evolution of hepatocellular carcinoma genomes in chimpanzees and humans

The rates and patterns of somatic mutations in normal and cancerous tissues remain largely unexplored outside of humans, despite their significance for understanding of aging and oncogenesis processes. The closest extant humans' relatives, chimpanzees (Pan troglodytes), have >98% genome sequence similarity with Homo sapiens, with every cancer-related gene having a close orthologue in the human genome, and yet the two species manifest strikingly different spectra of cancer types. To provide new insights into the evolution of cancer susceptibility and resistance from a comparative genomics perspective, we sequenced chimpanzee hepatocellular carcinoma (HCC) genomes and analyzed their mutational profiles in comparison with their human counterparts. Despite apparent histological similarities between human and chimpanzee HCCs, the HCC genomes in these two species exhibit strikingly divergent heterogeneity and adaptive evolution patterns. This study provides a comparative genomic perspective on how cancer evolves differently in humans and our closest living relatives.