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Unexpected Findings in Hereditary Breast and Ovarian Cancer Syndrome: Low-Level Constitutional Mosaicism in BRCA2

Hereditary breast and ovarian cancer syndrome (HBOC) is a clinical entity characterized by an increased risk of developing breast and ovarian cancer. The genetic diagnosis is based on the identification of heterozygous germinal variants in HBOC susceptibility genes. However, it has recently been des...

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Autores principales: Hidalgo Mayoral, Irene, Almeida Santiago, Ainhoa, Sánchez-Zapardiel, Jose Manuel, Hidalgo Calero, Beatriz, de la Hoya, Miguel, Gómez-Sanz, Alicia, de Miguel Reyes, Montserrat, Robles, Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9957471/
https://www.ncbi.nlm.nih.gov/pubmed/36833429
http://dx.doi.org/10.3390/genes14020502
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author Hidalgo Mayoral, Irene
Almeida Santiago, Ainhoa
Sánchez-Zapardiel, Jose Manuel
Hidalgo Calero, Beatriz
de la Hoya, Miguel
Gómez-Sanz, Alicia
de Miguel Reyes, Montserrat
Robles, Luis
author_facet Hidalgo Mayoral, Irene
Almeida Santiago, Ainhoa
Sánchez-Zapardiel, Jose Manuel
Hidalgo Calero, Beatriz
de la Hoya, Miguel
Gómez-Sanz, Alicia
de Miguel Reyes, Montserrat
Robles, Luis
author_sort Hidalgo Mayoral, Irene
collection PubMed
description Hereditary breast and ovarian cancer syndrome (HBOC) is a clinical entity characterized by an increased risk of developing breast and ovarian cancer. The genetic diagnosis is based on the identification of heterozygous germinal variants in HBOC susceptibility genes. However, it has recently been described that constitutional mosaic variants can contribute to the aetiology of HBOC. In constitutional mosaicism, individuals have at least two genotypically distinct populations of cells that arise from an early post-zygote event. The mutational event occurs early enough in development to affect several tissues. It is detected in germinal genetic studies as low variant allele frequency (VAF) variants (<30%) that are generally overlooked during the prioritization process. Constitutional mosaic variants can affect both somatic and germinal cells, and thus can be passed to the offspring and have important consequences for genetic counselling. In this work, we report the c.9648+1G>A mosaic variant in the BRCA2 gene and propose a diagnostic algorithm to deal with potential mosaic findings identified by Next Generation Sequencing (NGS).
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spelling pubmed-99574712023-02-25 Unexpected Findings in Hereditary Breast and Ovarian Cancer Syndrome: Low-Level Constitutional Mosaicism in BRCA2 Hidalgo Mayoral, Irene Almeida Santiago, Ainhoa Sánchez-Zapardiel, Jose Manuel Hidalgo Calero, Beatriz de la Hoya, Miguel Gómez-Sanz, Alicia de Miguel Reyes, Montserrat Robles, Luis Genes (Basel) Article Hereditary breast and ovarian cancer syndrome (HBOC) is a clinical entity characterized by an increased risk of developing breast and ovarian cancer. The genetic diagnosis is based on the identification of heterozygous germinal variants in HBOC susceptibility genes. However, it has recently been described that constitutional mosaic variants can contribute to the aetiology of HBOC. In constitutional mosaicism, individuals have at least two genotypically distinct populations of cells that arise from an early post-zygote event. The mutational event occurs early enough in development to affect several tissues. It is detected in germinal genetic studies as low variant allele frequency (VAF) variants (<30%) that are generally overlooked during the prioritization process. Constitutional mosaic variants can affect both somatic and germinal cells, and thus can be passed to the offspring and have important consequences for genetic counselling. In this work, we report the c.9648+1G>A mosaic variant in the BRCA2 gene and propose a diagnostic algorithm to deal with potential mosaic findings identified by Next Generation Sequencing (NGS). MDPI 2023-02-15 /pmc/articles/PMC9957471/ /pubmed/36833429 http://dx.doi.org/10.3390/genes14020502 Text en © 2023 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 Article
Hidalgo Mayoral, Irene
Almeida Santiago, Ainhoa
Sánchez-Zapardiel, Jose Manuel
Hidalgo Calero, Beatriz
de la Hoya, Miguel
Gómez-Sanz, Alicia
de Miguel Reyes, Montserrat
Robles, Luis
Unexpected Findings in Hereditary Breast and Ovarian Cancer Syndrome: Low-Level Constitutional Mosaicism in BRCA2
title Unexpected Findings in Hereditary Breast and Ovarian Cancer Syndrome: Low-Level Constitutional Mosaicism in BRCA2
title_full Unexpected Findings in Hereditary Breast and Ovarian Cancer Syndrome: Low-Level Constitutional Mosaicism in BRCA2
title_fullStr Unexpected Findings in Hereditary Breast and Ovarian Cancer Syndrome: Low-Level Constitutional Mosaicism in BRCA2
title_full_unstemmed Unexpected Findings in Hereditary Breast and Ovarian Cancer Syndrome: Low-Level Constitutional Mosaicism in BRCA2
title_short Unexpected Findings in Hereditary Breast and Ovarian Cancer Syndrome: Low-Level Constitutional Mosaicism in BRCA2
title_sort unexpected findings in hereditary breast and ovarian cancer syndrome: low-level constitutional mosaicism in brca2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9957471/
https://www.ncbi.nlm.nih.gov/pubmed/36833429
http://dx.doi.org/10.3390/genes14020502
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