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

Authors :
O'Mahony DG
Ramus SJ
Southey MC
Meagher NS
Hadjisavvas A
John EM
Hamann U
Imyanitov EN
Andrulis IL
Sharma P
Daly MB
Hake CR
Weitzel JN
Jakubowska A
Godwin AK
Arason A
Bane A
Simard J
Soucy P
Caligo MA
Mai PL
Claes KBM
Teixeira MR
Chung WK
Lazaro C
Hulick PJ
Toland AE
Pedersen IS
Neuhausen SL
Vega A
de la Hoya M
Nevanlinna H
Dhawan M
Zampiga V
Danesi R
Varesco L
Gismondi V
Vellone VG
James PA
Janavicius R
Nikitina-Zake L
Nielsen FC
van Overeem Hansen T
Pejovic T
Borg A
Rantala J
Offit K
Montagna M
Nathanson KL
Domchek SM
Osorio A
García MJ
Karlan BY
De Fazio A
Bowtell D
McGuffog L
Leslie G
Parsons MT
Dörk T
Speith LM
Dos Santos ES
da Costa AABA
Radice P
Peterlongo P
Papi L
Engel C
Hahnen E
Schmutzler RK
Wappenschmidt B
Easton DF
Tischkowitz M
Singer CF
Tan YY
Whittemore AS
Sieh W
Brenton JD
Yannoukakos D
Fostira F
Konstantopoulou I
Soukupova J
Vocka M
Chenevix-Trench G
Pharoah PDP
Antoniou AC
Goldgar DE
Spurdle AB
Michailidou K
Source :
British journal of cancer [Br J Cancer] 2023 Jun; Vol. 128 (12), pp. 2283-2294. Date of Electronic Publication: 2023 Apr 19.
Publication Year :
2023

Abstract

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.<br />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ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies.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).<br />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.<br />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.<br /> (© 2023. The Author(s).)

Details

Language :
English
ISSN :
1532-1827
Volume :
128
Issue :
12
Database :
MEDLINE
Journal :
British journal of cancer
Publication Type :
Academic Journal
Accession number :
37076566
Full Text :
https://doi.org/10.1038/s41416-023-02263-5