Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.
Naser Ansari-PourYonglan ZhengToshio F YoshimatsuAyodele SanniMustapha A AjaniJean-Baptiste ReynierAvraam TapinosJason J PittStefan DentroAnna WoodardPadma Sheila RajagopalDominic FitzgeraldAndreas J GruberAbayomi OdetundeAbiodun PopoolaAdeyinka G FalusiChinedum Peace BabalolaTemidayo OgundiranNasiru IbrahimJordi BarretinaPeter Van LooMengjie ChenKevin P WhiteOladosu OjengbedeJohn ObafunwaDezheng HuoDavid C WedgeOlufunmilayo I OlopadePublished in: Nature communications (2021)
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.
Keyphrases
- single cell
- rna seq
- copy number
- polycystic ovary syndrome
- dna repair
- dna damage
- pregnancy outcomes
- breast cancer risk
- end stage renal disease
- cervical cancer screening
- ejection fraction
- newly diagnosed
- cardiovascular events
- chronic kidney disease
- prognostic factors
- type diabetes
- pregnant women
- coronary artery disease
- adipose tissue
- high resolution
- gene expression
- dna methylation
- skeletal muscle
- papillary thyroid
- patient reported outcomes
- oxidative stress
- single molecule
- childhood cancer
- lymph node metastasis