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

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-021-27079-w

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
RDM
Role:
Author
ORCID:
0000-0003-0908-0484
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Role:
Author
ORCID:
0000-0001-6597-7072
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Role:
Author
ORCID:
0000-0003-2674-8159
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Role:
Author
ORCID:
0000-0001-5758-5773


Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
12
Issue:
1
Article number:
6946
Publication date:
2021-11-26
Acceptance date:
2021-11-02
DOI:
EISSN:
2041-1723
Pmid:
34836952


Language:
English
Keywords:
Pubs id:
1215112
Local pid:
pubs:1215112
Deposit date:
2021-12-04
ARK identifier:

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