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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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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). |
format | Online Article Text |
id | pubmed-9957471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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