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

Ansari-Pour, N.; Zheng, Y.; Pitt, J. J.; Dentro, S.; Yoshimatsu, T. F.; Sanni, A.; Ajani, M.; Woodard, A.; Rajagopal, P. S.; Fitzgerald, D.; Gruber, A. J.; Odetunde, A.; Popoola, A.; Falusi, A. G.; Babalola, C. P.; Ogundiran, T.; Obafunwa, J.; Ojengbede, O.; Ibrahim, N.; Barretina, J.; Van Loo, P.; Chen, M.; White, K. P.; Huo, D.; Wedge, D. C.; Olopade, O. I.

doi:10.1101/2020.10.28.359240

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bioRxiv · 10.1101/2020.10.28.359240

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

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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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Ansari-Pour, N., Zheng, Y., Pitt, J. J., Dentro, S., Yoshimatsu, T. F., Sanni, A., Ajani, M., Woodard, A., Rajagopal, P. S., Fitzgerald, D., Gruber, A. J., Odetunde, A., Popoola, A., Falusi, A. G., Babalola, C. P., Ogundiran, T., Obafunwa, J., Ojengbede, O., Ibrahim, N., Barretina, J., Van Loo, P., Chen, M., White, K. P., Huo, D., Wedge, D. C., Olopade, O. I.. 2020-10-28. Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes. https://doi.org/10.1101/2020.10.28.359240

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