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 Dentro, Anna Woodard, Padma Sheila Rajagopal, Dominic Fitzgerald, Andreas J. Gruber, Abayomi Odetunde, Abiodun Popoola, Adeyinka G. Falusi, Chinedum Peace Babalola, Temidayo Ogundiran, Nasiru Ibrahim, Jordi Barretina, Peter Van Loo, Mengjie Chen, Kevin P. White, Oladosu Ojengbede, John Obafunwa, Dezheng Huo, David C. Wedge () and Olufunmilayo I. Olopade ()
Additional contact information
Naser Ansari-Pour: University of Oxford
Yonglan Zheng: The University of Chicago
Toshio F. Yoshimatsu: The University of Chicago
Ayodele Sanni: Lagos State University Teaching Hospital, Ikeja
Mustapha Ajani: University of Ibadan
Jean-Baptiste Reynier: The University of Chicago
Avraam Tapinos: University of Manchester
Jason J. Pitt: National University of Singapore
Stefan Dentro: European Bioinformatics Institute
Anna Woodard: The University of Chicago
Padma Sheila Rajagopal: The University of Chicago
Dominic Fitzgerald: University of Chicago
Andreas J. Gruber: University of Oxford
Abayomi Odetunde: University of Ibadan
Abiodun Popoola: Lagos State University, Ikeja
Adeyinka G. Falusi: University of Ibadan
Chinedum Peace Babalola: University of Ibadan
Temidayo Ogundiran: University College Hospital
Nasiru Ibrahim: Lagos State University Teaching Hospital
Jordi Barretina: Hospital Universitari de Girona Dr Josep Trueta
Peter Van Loo: The Francis Crick Institute
Mengjie Chen: The University of Chicago
Kevin P. White: Tempus Labs Inc.
Oladosu Ojengbede: University of Ibadan
John Obafunwa: Lagos State University Teaching Hospital, Ikeja
Dezheng Huo: The University of Chicago
David C. Wedge: University of Oxford
Olufunmilayo I. Olopade: The University of Chicago

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-27079-w

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