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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2

Author

  • D.G. O’Mahony
  • A. Borg
  • Wendy K Chung

Summary, in English

Background: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system. Methods: Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong). Results: No histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis. Conclusions: We provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management. © 2023, The Author(s).

Department/s

  • LUCC: Lund University Cancer Centre
  • Familial Breast Cancer
  • Breastcancer-genetics

Publishing year

2023

Language

English

Pages

2283-2294

Publication/Series

British Journal of Cancer

Volume

128

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Familial Breast Cancer

ISBN/ISSN/Other

  • ISSN: 0007-0920