Sequencing for germline mutations in Swedish breast cancer families reveals novel breast cancer risk genes
Autor: | Jessada Thutkawkorapin, Annika Lindblom, Hafdis T. Helgadottir, Kristina Lagerstedt-Robinson |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Adult Candidate gene PALB2 Genetic counseling Science DNA Mutational Analysis Breast Neoplasms Biology Article 03 medical and health sciences 0302 clinical medicine Germline mutation Breast cancer Risk Factors Exome Sequencing medicine Genetics Humans Family Genetic Predisposition to Disease Gene Exome sequencing Germ-Line Mutation Cancer Sweden Multidisciplinary Cancer prevention DNA Helicases Middle Aged medicine.disease Pedigree 030104 developmental biology Codon Nonsense 030220 oncology & carcinogenesis Gain of Function Mutation Medicine Female Genes Neoplasm |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-7 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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