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Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes
Identifying genetic cancer risk factors will lead to improved genetic counseling, cancer prevention and cancer care. Analyzing families with a strong history of breast cancer (BC) has been a successful method to identify genes that contribute to the disease. This has led to discoveries of high-risk...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289997/ https://www.ncbi.nlm.nih.gov/pubmed/34282249 http://dx.doi.org/10.1038/s41598-021-94316-z |
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author | Helgadottir, Hafdis T. Thutkawkorapin, Jessada Lagerstedt-Robinson, Kristina Lindblom, Annika |
author_facet | Helgadottir, Hafdis T. Thutkawkorapin, Jessada Lagerstedt-Robinson, Kristina Lindblom, Annika |
author_sort | Helgadottir, Hafdis T. |
collection | PubMed |
description | Identifying genetic cancer risk factors will lead to improved genetic counseling, cancer prevention and cancer care. Analyzing families with a strong history of breast cancer (BC) has been a successful method to identify genes that contribute to the disease. This has led to discoveries of high-risk genes like the BRCA-genes. Nevertheless, many BC incidences are of unknown causes. In this study, exome sequencing on 59 BC patients from 24 Swedish families with a strong history of BC was performed to identify variants in known and novel BC predisposing genes. First, we screened known BC genes and identified two pathogenic variants in the BRIP1 and PALB2 genes. Secondly, to identify novel BC genes, rare and high impact variants and segregating in families were analyzed to identify 544 variants in novel BC candidate genes. Of those, 22 variants were defined as high-risk variants. Several interesting genes, either previously linked with BC or in pathways that when flawed could contribute to BC, were among the detected genes. The strongest candidates identified are the FANCM gene, involved in DNA double-strand break repair, and the RAD54L gene, involved in DNA recombination. Our study shows identifying pathogenic variants is challenging despite a strong family history of BC. Several interesting candidates were observed here that need to be further studied. |
format | Online Article Text |
id | pubmed-8289997 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82899972021-07-21 Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes Helgadottir, Hafdis T. Thutkawkorapin, Jessada Lagerstedt-Robinson, Kristina Lindblom, Annika Sci Rep Article Identifying genetic cancer risk factors will lead to improved genetic counseling, cancer prevention and cancer care. Analyzing families with a strong history of breast cancer (BC) has been a successful method to identify genes that contribute to the disease. This has led to discoveries of high-risk genes like the BRCA-genes. Nevertheless, many BC incidences are of unknown causes. In this study, exome sequencing on 59 BC patients from 24 Swedish families with a strong history of BC was performed to identify variants in known and novel BC predisposing genes. First, we screened known BC genes and identified two pathogenic variants in the BRIP1 and PALB2 genes. Secondly, to identify novel BC genes, rare and high impact variants and segregating in families were analyzed to identify 544 variants in novel BC candidate genes. Of those, 22 variants were defined as high-risk variants. Several interesting genes, either previously linked with BC or in pathways that when flawed could contribute to BC, were among the detected genes. The strongest candidates identified are the FANCM gene, involved in DNA double-strand break repair, and the RAD54L gene, involved in DNA recombination. Our study shows identifying pathogenic variants is challenging despite a strong family history of BC. Several interesting candidates were observed here that need to be further studied. Nature Publishing Group UK 2021-07-19 /pmc/articles/PMC8289997/ /pubmed/34282249 http://dx.doi.org/10.1038/s41598-021-94316-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Helgadottir, Hafdis T. Thutkawkorapin, Jessada Lagerstedt-Robinson, Kristina Lindblom, Annika Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes |
title | Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes |
title_full | Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes |
title_fullStr | Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes |
title_full_unstemmed | Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes |
title_short | Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes |
title_sort | sequencing for germline mutations in swedish breast cancer families reveals novel breast cancer risk genes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289997/ https://www.ncbi.nlm.nih.gov/pubmed/34282249 http://dx.doi.org/10.1038/s41598-021-94316-z |
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