The Clinical Utility of Next Generation Sequencing Results in a Community-Based Hereditary Cancer Risk Program

J Genet Couns. 2017 Feb;26(1):105-112. doi: 10.1007/s10897-016-9985-2. Epub 2016 Jun 9.


Since the 2013 Supreme Court ruling on BRCA1/BRCA2 patenting, hereditary cancer gene panels now include BRCA1 and BRCA2, making these panels an option for first-tier testing. However, questions remain about the clinical utility and implications of these panels for medical management with inclusion of genes of unknown to moderate penetrance. To better understand how use of these panels affected our practice, we reviewed patients who underwent testing in our clinic from July 1, 2013 through May 23, 2014. Indications for testing included personal and/or family history of breast and/or ovarian cancer. A total of 136 patients underwent panel testing via a single commercial laboratory; 12 (8.8 %) patients were positive for a pathogenic or likely pathogenic mutation (four BRCA2 mutations, two TP53 mutations, one CDH1 mutation, two ATM mutations, and one patient each with a CHEK2, NBN, or PALB2 mutation). Of these positive patients, 100 % met the National Comprehensive Cancer Network (NCCN) guidelines for Hereditary Breast and Ovarian Cancer genetic testing (2.2014). Mutations in seven of twelve (58 %) patients led to changes in medical management; three of seven (43 %) had a non-BRCA1 or BRCA2 gene mutation. Our findings suggest that there is clinical utility of panels that include genes of unknown to moderate penetrance.

Keywords: BRCA testing; Breast cancer; Cancer gene panel; Next-generation sequencing; Ovarian cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genes, Neoplasm / genetics*
  • Genetic Predisposition to Disease*
  • Genetic Testing / statistics & numerical data
  • High-Throughput Nucleotide Sequencing / statistics & numerical data*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Ovarian Neoplasms / genetics*
  • Sequence Analysis, DNA / statistics & numerical data