Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes
Jason J. Pitt,
Toshio F Yoshimatsu,
Padma Sheila Rajagopal,
Andreas J. Gruber,
Adeyinka G Falusi,
Chinedum Peace Babalola,
Peter Van Loo,
Kevin P White,
David C. Wedge,
Olufunmilayo I. Olopade
Posted 28 Oct 2020
bioRxiv DOI: 10.1101/2020.10.28.359240
Posted 28 Oct 2020
Black women of African ancestry 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 tumors, with RNA-seq in a subset, from indigenous African patients in Nigeria in comparison to The Cancer Genome Atlas (n=76) revealed a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations and a 10.5-year younger age at diagnosis. We also found evidence for non-coding mutations in two novel drivers (ZNF217 and SYPL1) and a novel INDEL signature strongly associated with African ancestry proportion. This comprehensive analysis of an understudied population underscores the need to incorporate diversity of genomes as a key parameter in fundamental research with potential to tailor clinical intervention and promote equity in precision oncology care. ### Competing Interest Statement K.P.W. is a Scientific Advisor and Fellow at Tempus. O.I.O is co-founder at CancerIQ and serves as Scientific Advisor at Tempus. All other authors declare no competing interest.
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