Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes
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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 Olufunmilayo I Olopade Toggle all authors (28)
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.
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Journal Nature Communications
Volume 12
Issue number 1
Pages 6946
Available online
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Publisher website (DOI) 10.1038/s41467-021-27079-w
Europe PubMed Central 34836952
Pubmed 34836952
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