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

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...

Descripción completa

Detalles Bibliográficos
Autores: O'Mahony, D.G., Ramus, S.J., Southey, M.C., Meagher, N.S., Hadjisavvas, A., John, E.M., Hamann, U., Imyanitov, E.N., Andrulis, I.L., Sharma, P., Daly, M.B., Hake, C.R., Weitzel, J.N., Jakubowska, A., Godwin, A.K., Arason, A., Bane, A., Simard, J., Soucy, P., Caligo, M.A., Mai, P.L., Claes, K.B.M., Teixeira, M.R., Chung, W.K., Lazaro, C., Hulick, P.J., Toland, A.E., Pedersen, I.S., Mourits, M.J.E., Neuhausen, S.L., Vega Gliemmo, Ana, de la Hoya, M., Nevanlinna, H., Dhawan, M., Zampiga, V., Danesi, R., Varesco, L., Gismondi, V., Vellone, V.G., James, P.A., Janavicius, R., Nikitina-Zake, L., Nielsen, F.C., van Overeem Hansen, T., Pejovic, T., Borg, A., Rantala, J., Offit, K., Montagna, M., Nathanson, K.L., Domchek, S.M., Osorio, A., García, M.J., Karlan, B.Y., Lesueur, F., De Fazio, A., Bowtell, D., McGuffog, L., Leslie, G., Parsons, M.T., Dörk, T., Speith, L.-M., dos Santos, E.S., da Costa, A.A.B.A., Radice, P., Peterlongo, P., Papi, L., Engel, C., Hahnen, E., Schmutzler, R.K., Wappenschmidt, B., Easton, D.F., Tischkowitz, M., Singer, C.F., Tan, Y.Y., Whittemore, A.S., Sieh, W., Brenton, J.D., Yannoukakos, D., Fostira, F., Konstantopoulou, I., Soukupova, J., Vocka, M., Chenevix-Trench, G., Pharoah, P.D.P., Antoniou, A.C., Goldgar, D.E., Spurdle, A.B., Michailidou, K.
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21822
Acceso en línea:https://portalcientifico.sergas.gal//documentos/64609f8ec6d6be6c90fc6db6
http://hdl.handle.net/20.500.11940/21822
Access Level:acceso abierto
Palabra clave:Humans
Female
Virulence
BRCA1 Protein
BRCA2 Protein
Ovarian Neoplasms
Genetic Predisposition to Disease
Breast Neoplasms
FPGMX
Descripción
Sumario: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.

Similares en LA Referencia