Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes

Abstract 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 h...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hafdis T. Helgadottir, Jessada Thutkawkorapin, Kristina Lagerstedt-Robinson, Annika Lindblom
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/91c5989be8644f0ab7d8dfce646b1eff
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:91c5989be8644f0ab7d8dfce646b1eff
record_format	dspace
spelling	oai:doaj.org-article:91c5989be8644f0ab7d8dfce646b1eff2021-12-02T16:26:30ZSequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes10.1038/s41598-021-94316-z2045-2322https://doaj.org/article/91c5989be8644f0ab7d8dfce646b1eff2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94316-zhttps://doaj.org/toc/2045-2322Abstract 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.Hafdis T. HelgadottirJessada ThutkawkorapinKristina Lagerstedt-RobinsonAnnika LindblomNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hafdis T. Helgadottir Jessada Thutkawkorapin Kristina Lagerstedt-Robinson Annika Lindblom Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes
description	Abstract 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	article
author	Hafdis T. Helgadottir Jessada Thutkawkorapin Kristina Lagerstedt-Robinson Annika Lindblom
author_facet	Hafdis T. Helgadottir Jessada Thutkawkorapin Kristina Lagerstedt-Robinson Annika Lindblom
author_sort	Hafdis T. Helgadottir
title	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_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_sort	sequencing for germline mutations in swedish breast cancer families reveals novel breast cancer risk genes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/91c5989be8644f0ab7d8dfce646b1eff
work_keys_str_mv	AT hafdisthelgadottir sequencingforgermlinemutationsinswedishbreastcancerfamiliesrevealsnovelbreastcancerriskgenes AT jessadathutkawkorapin sequencingforgermlinemutationsinswedishbreastcancerfamiliesrevealsnovelbreastcancerriskgenes AT kristinalagerstedtrobinson sequencingforgermlinemutationsinswedishbreastcancerfamiliesrevealsnovelbreastcancerriskgenes AT annikalindblom sequencingforgermlinemutationsinswedishbreastcancerfamiliesrevealsnovelbreastcancerriskgenes
_version_	1718384068042686464

Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes

Ejemplares similares