Challenges in Interpreting Germline Mutations in BARD1 and ATM in Breast and Ovarian Cancer Patients

Breast J. 2017 Jul;23(4):461-464. doi: 10.1111/tbj.12764. Epub 2017 Jan 31.

Abstract

Next-generation sequencing promotes identification of mutations in non-BRCA1/2 genes in hereditary cancer families. The contribution of mutations in moderate penetrance genes to hereditary cancer risk is not well established. Here, we report a family with early onset breast and fallopian tube cancer that was identified as carrying germline mutations in BARD1 and ATM genes. Loss of heterozygosity studies suggest a causative role of the BARD1 mutation in the development of primary peritoneal cancer, but fail to confirm an association between germline ATM mutations and breast cancer development in this family. Complexities in interpreting implications of mutations in moderate-risk cancer susceptibility genes are discussed.

Keywords: ATM; BARD1; breast cancer; ovarian cancer; primary peritoneal cancer.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Breast Neoplasms / genetics*
  • Diagnosis, Differential
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Mutation
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Tumor Suppressor Proteins / genetics*
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Tumor Suppressor Proteins
  • BARD1 protein, human
  • Ubiquitin-Protein Ligases
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins