Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

Autor: Pitt JJ; Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA.; Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Singapore, 117599, Singapore., Riester M; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Zheng Y; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA., Yoshimatsu TF; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA., Sanni A; Department of Pathology and Forensic Medicine, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria., Oluwasola O; Department of Pathology, University of Ibadan, Ibadan, Oyo, Nigeria., Veloso A; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Labrot E; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Wang S; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.; Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China., Odetunde A; Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria., Ademola A; Department of Surgery, University of Ibadan, Ibadan, Oyo, Nigeria., Okedere B; Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria., Mahan S; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Leary R; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Macomber M; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Ajani M; Department of Pathology, University of Ibadan, Ibadan, Oyo, Nigeria., Johnson RS; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Fitzgerald D; Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA., Grundstad AJ; Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA., Tuteja JH; Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA., Khramtsova G; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA., Zhang J; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA., Sveen E; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA., Hwang B; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Clayton W; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA., Nkwodimmah C; Department of Surgery, University of Ibadan, Ibadan, Oyo, Nigeria., Famooto B; Department of Surgery, University of Ibadan, Ibadan, Oyo, Nigeria., Obasi E; Department of Pathology and Forensic Medicine, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria., Aderoju V; Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria., Oludara M; Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria., Omodele F; Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria., Akinyele O; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA., Adeoye A; Department of Pathology, University of Ibadan, Ibadan, Oyo, Nigeria., Ogundiran T; Department of Surgery, University of Ibadan, Ibadan, Oyo, Nigeria., Babalola C; Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria.; Department of Pharmaceutical Chemistry, University of Ibadan, Ibadan, Oyo, Nigeria., MacIsaac K; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Popoola A; Oncology Unit, Department of Radiology, Lagos State University, Ikeja, Lagos, Nigeria., Morrissey MP; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Chen LS; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA., Wang J; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA., Olopade CO; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA., Falusi AG; Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria., Winckler W; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Haase K; The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Van Loo P; The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.; Department of Human Genetics, University of Leuven, Oude Markt 13, Leuven, 3000, Belgium., Obafunwa J; Department of Pathology and Forensic Medicine, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria., Papoutsakis D; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Ojengbede O; Centre for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria., Weber B; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA., Ibrahim N; Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria., White KP; Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA. kpwhite@uchicago.edu.; Tempus Labs Inc., Chicago, IL, USA. kpwhite@uchicago.edu., Huo D; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. dhuo@health.bsd.uchicago.edu.; Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA. dhuo@health.bsd.uchicago.edu., Olopade OI; Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA. folopade@medicine.bsd.uchicago.edu.; Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. folopade@medicine.bsd.uchicago.edu., Barretina J; Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA. jordi.barretina@gmail.com.; Girona Biomedical Research Institute (IDIBGI), Girona, 17007, Spain. jordi.barretina@gmail.com.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Oct 16; Vol. 9 (1), pp. 4181. Date of Electronic Publication: 2018 Oct 16.
DOI: 10.1038/s41467-018-06616-0
Abstrakt: 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. PLK2, KDM6A, 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.
Databáze: MEDLINE
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