Discovery of mutations in homologous recombination genes in African-American women with breast cancer

Yuan Chun Ding, Aaron W. Adamson, Linda Steele, Adam M. Bailis, Esther M. John, Gail Tomlinson, Susan L. Neuhausen

Research output: Contribution to journalArticle

Abstract

African-American women are more likely to develop aggressive breast cancer at younger ages and experience poorer cancer prognoses than non-Hispanic Caucasians. Deficiency in repair of DNA by homologous recombination (HR) is associated with cancer development, suggesting that mutations in genes that affect this process may cause breast cancer. Inherited pathogenic mutations have been identified in genes involved in repairing DNA damage, but few studies have focused on African-Americans. We screened for germline mutations in seven HR repair pathway genes in DNA of 181 African-American women with breast cancer, evaluated the potential effects of identified missense variants using in silico prediction software, and functionally characterized a set of missense variants by yeast two-hybrid assays. We identified five likely-damaging variants, including two PALB2 truncating variants (Q151X and W1038X) and three novel missense variants (RAD51C C135R, and XRCC3 L297P and V337E) that abolish protein–protein interactions in yeast two-hybrid assays. Our results add to evidence that HR gene mutations account for a proportion of the genetic risk for developing breast cancer in African-Americans. Identifying additional mutations that diminish HR may provide a tool for better assessing breast cancer risk and improving approaches for targeted treatment.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalFamilial Cancer
DOIs
StateAccepted/In press - Sep 2 2017

Fingerprint

Homologous Recombination
African Americans
Breast Neoplasms
Mutation
Recombinational DNA Repair
Two-Hybrid System Techniques
Genes
Germ-Line Mutation
Computer Simulation
DNA Damage
Neoplasms
Software
DNA

Keywords

  • African-Americans
  • Breast cancer
  • Germline mutations
  • Homologous recombination
  • Loss of protein function

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Ding, Y. C., Adamson, A. W., Steele, L., Bailis, A. M., John, E. M., Tomlinson, G., & Neuhausen, S. L. (Accepted/In press). Discovery of mutations in homologous recombination genes in African-American women with breast cancer. Familial Cancer, 1-9. https://doi.org/10.1007/s10689-017-0036-4

Discovery of mutations in homologous recombination genes in African-American women with breast cancer. / Ding, Yuan Chun; Adamson, Aaron W.; Steele, Linda; Bailis, Adam M.; John, Esther M.; Tomlinson, Gail; Neuhausen, Susan L.

In: Familial Cancer, 02.09.2017, p. 1-9.

Research output: Contribution to journalArticle

Ding, Yuan Chun ; Adamson, Aaron W. ; Steele, Linda ; Bailis, Adam M. ; John, Esther M. ; Tomlinson, Gail ; Neuhausen, Susan L. / Discovery of mutations in homologous recombination genes in African-American women with breast cancer. In: Familial Cancer. 2017 ; pp. 1-9.
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