Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies. Breast cancer heterogeneity and tumour evolutionary trajectories remain largely unknown among women of African ancestry. Here, the authors perform whole genome and transcriptome sequencing of Nigerian breast cancer patients and identify unique evolutionary phenomena.

Automated summary

Research reveals higher genomic instability and intra-tumoral heterogeneity in Nigerian breast cancer patients, as well as early clonal GATA3 mutations and a unique INDEL signature associated with African ancestry. Characterizing tumors for homologous recombination deficiency is shown to have significant clinical relevance, underscoring the importance of including diverse populations in biomedical research. This study sheds light on the unknown breast cancer heterogeneity and tumour evolutionary trajectories among women of African ancestry.