TY - JOUR
T1 - Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes
AU - Ansari-pour, Naser
AU - Zheng, Yonglan
AU - F. Yoshimatsu, Toshio
AU - Sanni, Ayodele
AU - Ajani, Mustapha
AU - Reynier, Jean-Baptiste
AU - Tapinos, Avraam
AU - J. Pitt, Jason
AU - Dentro, Stefan
AU - Woodard, Anna
AU - Sheila Rajagopal, Padma
AU - Fitzgerald, Dominic
AU - Gruber, Andreas
AU - Odetunde, Abayomi
AU - Popoola, Abiodun
AU - Falusi, Adeyinka
AU - Peace Babalola, Chinedum
AU - Ogundiran, Temidayo
AU - Ibrahim, Nasiru
AU - Barretina, Jordi
AU - Van Loo, Peter
AU - Chen, Mengjie
AU - P. White, Kevin
AU - Ojengbede, Oladosu
AU - Obafunwa, John
AU - Huo, Dezheng
AU - Wedge, David
AU - Olopade, Olufunmilayo I
PY - 2021/11/26
Y1 - 2021/11/26
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-021-27079-w
DO - 10.1038/s41467-021-27079-w
M3 - Article
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
M1 - 6946
ER -
