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

Naser Ansari‐Pour; Yonglan Zheng; Toshio F. Yoshimatsu; Ayodele Sanni; Mustapha Ajani; Jean-Baptiste Reynier; Avraam Tapinos; Jason J. Pitt; Stefan C. Dentro; Anna Woodard; Padma Sheila Rajagopal; Dominic Fitzgerald; Andreas J Gruber; Abayomi Odetunde; Abiodun Olaniyi Popoola; Adeyinka Gladys Falusi; Chinedum Peace Babalola; Temidayo Olusade Ogundiran; Nasiru Akanmu Ibrahim; Jordi G Barretina; Peter Van Loo; Mengjie Chen; Kevin P. White; Oladosu Akanbi Ojengbede; John Oladapo Obafunwa; Dezheng Huo; David C. Wedge; Olufunmilayo Ibironke Olopade

doi:10.1038/s41467-021-27079-w

GenomicsNature CommunicationsNov 26, 2021

Peer-reviewed journal article

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

Naser Ansari‐Pour iD, Yonglan Zheng iD, Toshio F. Yoshimatsu iD, Ayodele Sanni, Mustapha Ajani iD, Jean-Baptiste Reynier, Avraam Tapinos iD, Jason J. Pitt iD, Stefan C. Dentro iD, Anna Woodard, Padma Sheila Rajagopal iD, Dominic Fitzgerald iD, Andreas J Gruber iD, Abayomi Odetunde iD, Abiodun Olaniyi Popoola iD, Adeyinka Gladys Falusi iD, Chinedum Peace Babalola iD, Temidayo Olusade Ogundiran iD, Nasiru Akanmu Ibrahim, Jordi G Barretina iD, Peter Van Loo iD, Mengjie Chen iD, Kevin P. White iD, Oladosu Akanbi Ojengbede iD, John Oladapo Obafunwa iD, , Olufunmilayo Ibironke Olopade iD

Abstract

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.

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