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

Nat Commun. 2018 Oct 16;9(1):4181. doi: 10.1038/s41467-018-06616-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC Deaminases / genetics
  • African Americans / genetics
  • Antigens, CD / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Cadherins / genetics
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • European Continental Ancestry Group / genetics
  • Exome
  • Female
  • Homologous Recombination*
  • Humans
  • Mutation*
  • Nigeria
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Whole Genome Sequencing

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • APOBEC Deaminases