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Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.
Ansari-Pour, Naser; Zheng, Yonglan; Yoshimatsu, Toshio F; Sanni, Ayodele; Ajani, Mustapha; Reynier, Jean-Baptiste; Tapinos, Avraam; Pitt, Jason J; Dentro, Stefan; Woodard, Anna; Rajagopal, Padma Sheila; Fitzgerald, Dominic; Gruber, Andreas J; Odetunde, Abayomi; Popoola, Abiodun; Falusi, Adeyinka G; Babalola, Chinedum Peace; Ogundiran, Temidayo; Ibrahim, Nasiru; Barretina, Jordi; Van Loo, Peter; Chen, Mengjie; White, Kevin P; Ojengbede, Oladosu; Obafunwa, John; Huo, Dezheng; Wedge, David C; Olopade, Olufunmilayo I.
Afiliación
  • Ansari-Pour N; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7LF, UK.
  • Zheng Y; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Yoshimatsu TF; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
  • Sanni A; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
  • Ajani M; Department of Pathology and Forensic Medicine, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.
  • Reynier JB; Department of Pathology, University of Ibadan, Ibadan, Oyo, Nigeria.
  • Tapinos A; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
  • Pitt JJ; Manchester Cancer Research Centre, University of Manchester, Manchester, M20 4GJ, UK.
  • Dentro S; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
  • Woodard A; European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, CB10 1SD, UK.
  • Rajagopal PS; Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
  • Fitzgerald D; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
  • Gruber AJ; Department of Computer Science, The University of Chicago, Chicago, IL, 60637, USA.
  • Odetunde A; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
  • Popoola A; Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL, 60637, USA.
  • Falusi AG; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7LF, UK.
  • Babalola CP; Manchester Cancer Research Centre, University of Manchester, Manchester, M20 4GJ, UK.
  • Ogundiran T; Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria.
  • Ibrahim N; Oncology Unit, Department of Radiology, Lagos State University, Ikeja, Lagos, Nigeria.
  • Barretina J; Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria.
  • Van Loo P; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Oyo, Nigeria.
  • Chen M; Department of Surgery, University College Hospital, Ibadan, Oyo, Nigeria.
  • White KP; Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.
  • Ojengbede O; Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain.
  • Obafunwa J; The Francis Crick Institute, London, NW1 1AT, UK.
  • Huo D; Department of Human Genetics, The University of Chicago, Chicago, IL, 60637, USA.
  • Wedge DC; Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
  • Olopade OI; Tempus Labs Inc., Chicago, IL, 60654, USA.
Nat Commun ; 12(1): 6946, 2021 11 26.
Article en En | MEDLINE | ID: mdl-34836952
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Biomarcadores de Tumor / Disparidades en el Estado de Salud / Evolución Clonal Tipo de estudio: Etiology_studies / Observational_studies / Risk_factors_studies Aspecto: Determinantes_sociais_saude / Equity_inequality / Patient_preference Límite: Adult / Aged / Female / Humans / Middle aged País/Región como asunto: Africa Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Biomarcadores de Tumor / Disparidades en el Estado de Salud / Evolución Clonal Tipo de estudio: Etiology_studies / Observational_studies / Risk_factors_studies Aspecto: Determinantes_sociais_saude / Equity_inequality / Patient_preference Límite: Adult / Aged / Female / Humans / Middle aged País/Región como asunto: Africa Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido