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Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing?

The probability of carrying two pathogenic variants (PVs) in dominant cancer-predisposing genes for hereditary breast and ovarian cancer and lynch syndromes in the same patient is uncommon, except in populations where founder effects exist. Two breast cancer women that are double heterozygotes (DH)...

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Autores principales: Infante, Mar, Arranz-Ledo, Mónica, Lastra, Enrique, Abella, Luis Enrique, Ferreira, Raquel, Orozco, Marta, Hernández, Lara, Martínez, Noemí, Durán, Mercedes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570103/
https://www.ncbi.nlm.nih.gov/pubmed/36232793
http://dx.doi.org/10.3390/ijms231911499
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author Infante, Mar
Arranz-Ledo, Mónica
Lastra, Enrique
Abella, Luis Enrique
Ferreira, Raquel
Orozco, Marta
Hernández, Lara
Martínez, Noemí
Durán, Mercedes
author_facet Infante, Mar
Arranz-Ledo, Mónica
Lastra, Enrique
Abella, Luis Enrique
Ferreira, Raquel
Orozco, Marta
Hernández, Lara
Martínez, Noemí
Durán, Mercedes
author_sort Infante, Mar
collection PubMed
description The probability of carrying two pathogenic variants (PVs) in dominant cancer-predisposing genes for hereditary breast and ovarian cancer and lynch syndromes in the same patient is uncommon, except in populations where founder effects exist. Two breast cancer women that are double heterozygotes (DH) for both BRCA1/BRCA2, one ovarian cancer case DH for BRCA1/RAD51C, and another breast and colorectal cancer who is DH for BRCA2/PMS2 were identified in our cohort. Ages at diagnosis and severity of disease in BRCA1/BRCA2 DH resembled BRCA1 single-carrier features. Similarly, the co-existence of the BRCA2 and PMS2 mutations prompted the development of breast and colorectal cancer in the same patient. The first BRCA1/BRCA2 DH was identified by HA-based and Sanger sequencing (1 of 623 families with BRCA PVs). However, this ratio has increased up to 2.9% (1 DH carrier vs. 103 single PV carriers) since using a custom 35-cancer gene on-demand panel. The type of cancer developed in each DH patient was consistent with the independently inherited condition, and the clinical outcome was no worse than in patients with single BRCA1 mutations. Therefore, the clinical impact, especially in patients with two hereditary syndromes, lies in genetic counseling tailor-made for each family based on the clinical guidelines for each syndrome. The number of DH is expected to be increased in the future as a result of next generation sequencing routines.
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spelling pubmed-95701032022-10-17 Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing? Infante, Mar Arranz-Ledo, Mónica Lastra, Enrique Abella, Luis Enrique Ferreira, Raquel Orozco, Marta Hernández, Lara Martínez, Noemí Durán, Mercedes Int J Mol Sci Case Report The probability of carrying two pathogenic variants (PVs) in dominant cancer-predisposing genes for hereditary breast and ovarian cancer and lynch syndromes in the same patient is uncommon, except in populations where founder effects exist. Two breast cancer women that are double heterozygotes (DH) for both BRCA1/BRCA2, one ovarian cancer case DH for BRCA1/RAD51C, and another breast and colorectal cancer who is DH for BRCA2/PMS2 were identified in our cohort. Ages at diagnosis and severity of disease in BRCA1/BRCA2 DH resembled BRCA1 single-carrier features. Similarly, the co-existence of the BRCA2 and PMS2 mutations prompted the development of breast and colorectal cancer in the same patient. The first BRCA1/BRCA2 DH was identified by HA-based and Sanger sequencing (1 of 623 families with BRCA PVs). However, this ratio has increased up to 2.9% (1 DH carrier vs. 103 single PV carriers) since using a custom 35-cancer gene on-demand panel. The type of cancer developed in each DH patient was consistent with the independently inherited condition, and the clinical outcome was no worse than in patients with single BRCA1 mutations. Therefore, the clinical impact, especially in patients with two hereditary syndromes, lies in genetic counseling tailor-made for each family based on the clinical guidelines for each syndrome. The number of DH is expected to be increased in the future as a result of next generation sequencing routines. MDPI 2022-09-29 /pmc/articles/PMC9570103/ /pubmed/36232793 http://dx.doi.org/10.3390/ijms231911499 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Infante, Mar
Arranz-Ledo, Mónica
Lastra, Enrique
Abella, Luis Enrique
Ferreira, Raquel
Orozco, Marta
Hernández, Lara
Martínez, Noemí
Durán, Mercedes
Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing?
title Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing?
title_full Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing?
title_fullStr Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing?
title_full_unstemmed Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing?
title_short Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing?
title_sort increased co-occurrence of pathogenic variants in hereditary breast and ovarian cancer and lynch syndromes: a consequence of multigene panel genetic testing?
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570103/
https://www.ncbi.nlm.nih.gov/pubmed/36232793
http://dx.doi.org/10.3390/ijms231911499
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