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Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features. (Nat Commun, Oct 2018)

Pitt JJ1,2, Riester M3, Zheng Y4, Yoshimatsu TF4, Sanni A5, Oluwasola O6, Veloso A3, Labrot E3, Wang S4,7, Odetunde A8, Ademola A9, Okedere B8, Mahan S3, Leary R3, Macomber M3, Ajani M6, Johnson RS3, Fitzgerald D1, Grundstad AJ1, Tuteja JH1, Khramtsova G4, Zhang J4, Sveen E4, Hwang B3, Clayton W4, Nkwodimmah C9, Famooto B9, Obasi E5, Aderoju V10, Oludara M10, Omodele F10, Akinyele O4, Adeoye A6, Ogundiran T9, Babalola C8,11, MacIsaac K3, Popoola A12, Morrissey MP3, Chen LS13, Wang J13, Olopade CO4, Falusi AG8, Winckler W3, Haase K14, Van Loo P14,15, Obafunwa J5, Papoutsakis D3, Ojengbede O16, Weber B3, Ibrahim N10, White KP17, Huo D18,19, Olopade OI20,21, Barretina J22,23.

Author information
1Institute for Genomics and Systems Biology, University of Chicago, Chicago, USA
2Cancer Science Institute of Singapore, National University of Singapore, Singapore.
3Novartis Institutes for BioMedical Research, Cambridge, USA.
4Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, USA.
5Department of Pathology and Forensic Medicine, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.
6Department of Pathology, University of Ibadan, Ibadan, Oyo, Nigeria.
7Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
8Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria.
9Department of Surgery, University of Ibadan, Ibadan, Oyo, Nigeria.
10Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.
11Department of Pharmaceutical Chemistry, University of Ibadan, Ibadan, Oyo, Nigeria.
12Oncology Unit, Department of Radiology, Lagos State University, Ikeja, Lagos, Nigeria.
13Department of Public Health Sciences, University of Chicago, Chicago, USA.
14The Francis Crick Institute, London, UK.
15Department of Human Genetics, University of Leuven, Leuven, Belgium.
16Centre for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria.
17Institute for Genomics and Systems Biology, University of Chicago, Chicago, USA.
18Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, USA.
19Department of Public Health Sciences, University of Chicago, Chicago, USA.
20Institute for Genomics and Systems Biology, University of Chicago, Chicago, USA.
21Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, USA.
22Novartis Institutes for BioMedical Research, Cambridge, USA.
23Girona Biomedical Research Institute (IDIBGI), Girona, Spain.

Abstract
Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 − tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation—indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.

PMID: 30327465