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

Author

Listed:
  • Naser Ansari-Pour

    (University of Oxford
    University of Oxford)

  • Yonglan Zheng

    (The University of Chicago)

  • Toshio F. Yoshimatsu

    (The University of Chicago)

  • Ayodele Sanni

    (Lagos State University Teaching Hospital, Ikeja)

  • Mustapha Ajani

    (University of Ibadan)

  • Jean-Baptiste Reynier

    (The University of Chicago)

  • Avraam Tapinos

    (University of Manchester)

  • Jason J. Pitt

    (National University of Singapore)

  • Stefan Dentro

    (European Bioinformatics Institute
    Wellcome Trust Sanger Institute, Hinxton)

  • Anna Woodard

    (The University of Chicago
    The University of Chicago)

  • Padma Sheila Rajagopal

    (The University of Chicago)

  • Dominic Fitzgerald

    (University of Chicago)

  • Andreas J. Gruber

    (University of Oxford
    University of Manchester)

  • Abayomi Odetunde

    (University of Ibadan)

  • Abiodun Popoola

    (Lagos State University, Ikeja)

  • Adeyinka G. Falusi

    (University of Ibadan)

  • Chinedum Peace Babalola

    (University of Ibadan)

  • Temidayo Ogundiran

    (University College Hospital)

  • Nasiru Ibrahim

    (Lagos State University Teaching Hospital)

  • Jordi Barretina

    (Hospital Universitari de Girona Dr Josep Trueta)

  • Peter Van Loo

    (The Francis Crick Institute)

  • Mengjie Chen

    (The University of Chicago
    The University of Chicago)

  • Kevin P. White

    (Tempus Labs Inc.)

  • Oladosu Ojengbede

    (University of Ibadan)

  • John Obafunwa

    (Lagos State University Teaching Hospital, Ikeja)

  • Dezheng Huo

    (The University of Chicago)

  • David C. Wedge

    (University of Oxford
    University of Manchester)

  • Olufunmilayo I. Olopade

    (The University of Chicago)

Abstract

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.

Suggested Citation

  • Naser Ansari-Pour & Yonglan Zheng & Toshio F. Yoshimatsu & Ayodele Sanni & Mustapha Ajani & Jean-Baptiste Reynier & Avraam Tapinos & Jason J. Pitt & Stefan Dentro & Anna Woodard & Padma Sheila Rajagop, 2021. "Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27079-w
    DOI: 10.1038/s41467-021-27079-w
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