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

Author

Listed:
  • Jason J. Pitt

    (University of Chicago
    National University of Singapore)

  • Markus Riester

    (Novartis Institutes for BioMedical Research)

  • Yonglan Zheng

    (University of Chicago)

  • Toshio F. Yoshimatsu

    (University of Chicago)

  • Ayodele Sanni

    (Lagos State University Teaching Hospital)

  • Olayiwola Oluwasola

    (University of Ibadan)

  • Artur Veloso

    (Novartis Institutes for BioMedical Research)

  • Emma Labrot

    (Novartis Institutes for BioMedical Research)

  • Shengfeng Wang

    (University of Chicago
    Peking University Health Science Center)

  • Abayomi Odetunde

    (University of Ibadan)

  • Adeyinka Ademola

    (University of Ibadan)

  • Babajide Okedere

    (University of Ibadan)

  • Scott Mahan

    (Novartis Institutes for BioMedical Research)

  • Rebecca Leary

    (Novartis Institutes for BioMedical Research)

  • Maura Macomber

    (Novartis Institutes for BioMedical Research)

  • Mustapha Ajani

    (University of Ibadan)

  • Ryan S. Johnson

    (Novartis Institutes for BioMedical Research)

  • Dominic Fitzgerald

    (University of Chicago)

  • A. Jason Grundstad

    (University of Chicago)

  • Jigyasa H. Tuteja

    (University of Chicago)

  • Galina Khramtsova

    (University of Chicago)

  • Jing Zhang

    (University of Chicago)

  • Elisabeth Sveen

    (University of Chicago)

  • Bryce Hwang

    (Novartis Institutes for BioMedical Research)

  • Wendy Clayton

    (University of Chicago)

  • Chibuzor Nkwodimmah

    (University of Ibadan)

  • Bisola Famooto

    (University of Ibadan)

  • Esther Obasi

    (Lagos State University Teaching Hospital)

  • Victor Aderoju

    (Lagos State University Teaching Hospital)

  • Mobolaji Oludara

    (Lagos State University Teaching Hospital)

  • Folusho Omodele

    (Lagos State University Teaching Hospital)

  • Odunayo Akinyele

    (University of Chicago)

  • Adewunmi Adeoye

    (University of Ibadan)

  • Temidayo Ogundiran

    (University of Ibadan)

  • Chinedum Babalola

    (University of Ibadan
    University of Ibadan)

  • Kenzie MacIsaac

    (Novartis Institutes for BioMedical Research)

  • Abiodun Popoola

    (Lagos State University)

  • Michael P. Morrissey

    (Novartis Institutes for BioMedical Research)

  • Lin S. Chen

    (University of Chicago)

  • Jiebiao Wang

    (University of Chicago)

  • Christopher O. Olopade

    (University of Chicago)

  • Adeyinka G. Falusi

    (University of Ibadan)

  • Wendy Winckler

    (Novartis Institutes for BioMedical Research)

  • Kerstin Haase

    (The Francis Crick Institute)

  • Peter Loo

    (The Francis Crick Institute
    University of Leuven)

  • John Obafunwa

    (Lagos State University Teaching Hospital)

  • Dimitris Papoutsakis

    (Novartis Institutes for BioMedical Research)

  • Oladosu Ojengbede

    (University of Ibadan)

  • Barbara Weber

    (Novartis Institutes for BioMedical Research)

  • Nasiru Ibrahim

    (Lagos State University Teaching Hospital)

  • Kevin P. White

    (University of Chicago
    Tempus Labs Inc.)

  • Dezheng Huo

    (University of Chicago
    University of Chicago)

  • Olufunmilayo I. Olopade

    (University of Chicago
    University of Chicago)

  • Jordi Barretina

    (Novartis Institutes for BioMedical Research
    Girona Biomedical Research Institute (IDIBGI))

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. 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.

Suggested Citation

  • Jason J. Pitt & Markus Riester & Yonglan Zheng & Toshio F. Yoshimatsu & Ayodele Sanni & Olayiwola Oluwasola & Artur Veloso & Emma Labrot & Shengfeng Wang & Abayomi Odetunde & Adeyinka Ademola & Babaji, 2018. "Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06616-0
    DOI: 10.1038/s41467-018-06616-0
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    Cited by:

    1. 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.

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