Clinical validity assessment of genes frequently tested on hereditary breast and ovarian cancer susceptibility sequencing panels

Kristy Lee, Bryce A. Seifert, Hermela Shimelis, Rajarshi Ghosh, Stephanie B. Crowley, Natalie J. Carter, Kurston Doonanco, A. Katherine Foreman, Deborah I. Ritter, Sharisse Jimenez, Mackenzie Trapp, Kenneth Offit, Sharon E. Plon, Fergus J Couch

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Purpose: Several genes on hereditary breast and ovarian cancer susceptibility test panels have not been systematically examined for strength of association with disease. We employed the Clinical Genome Resource (ClinGen) clinical validity framework to assess the strength of evidence between selected genes and breast or ovarian cancer. Methods: Thirty-one genes offered on cancer panel testing were selected for evaluation. The strength of gene–disease relationship was systematically evaluated and a clinical validity classification of either Definitive, Strong, Moderate, Limited, Refuted, Disputed, or No Reported Evidence was assigned. Results: Definitive clinical validity classifications were made for 10/31 and 10/32 gene–disease pairs for breast and ovarian cancer respectively. Two genes had a Moderate classification whereas, 6/31 and 6/32 genes had Limited classifications for breast and ovarian cancer respectively. Contradictory evidence resulted in Disputed or Refuted assertions for 9/31 genes for breast and 4/32 genes for ovarian cancer. No Reported Evidence of disease association was asserted for 5/31 genes for breast and 11/32 for ovarian cancer. Conclusion: Evaluation of gene–disease association using the ClinGen clinical validity framework revealed a wide range of classifications. This information should aid laboratories in tailoring appropriate gene panels and assist health-care providers in interpreting results from panel testing.

Original languageEnglish (US)
JournalGenetics in Medicine
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • classification
  • ClinGen
  • gene test panels
  • gene validity
  • hereditary breast and ovarian cancer

ASJC Scopus subject areas

  • Genetics(clinical)

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    Lee, K., Seifert, B. A., Shimelis, H., Ghosh, R., Crowley, S. B., Carter, N. J., Doonanco, K., Foreman, A. K., Ritter, D. I., Jimenez, S., Trapp, M., Offit, K., Plon, S. E., & Couch, F. J. (Accepted/In press). Clinical validity assessment of genes frequently tested on hereditary breast and ovarian cancer susceptibility sequencing panels. Genetics in Medicine. https://doi.org/10.1038/s41436-018-0361-5