The results of multigene panel sequencing in Slovak HBOC families
| Autor: | Marian Baldovic, Lenka Wachsmannova, Andrea Patlevicova, Sona Ciernikova, Petra Tilandyova, Juraj Krajcovic, Jan Markus, Klaudia Kosova, Michal Konecny |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Ovarian Neoplasms
Genetics Slovakia Cancer Research Mutation PALB2 Genes BRCA1 Cancer Breast Neoplasms Biology medicine.disease_cause medicine.disease Penetrance Oncology MUTYH medicine Hereditary Breast and Ovarian Cancer Syndrome Humans Female Genetic Predisposition to Disease Multiplex ligation-dependent probe amplification Family history skin and connective tissue diseases CHEK2 |
| Zdroj: | Neoplasma. 68:652-664 |
| ISSN: | 1338-4317 |
| DOI: | 10.4149/neo_2021_201204n1307 |
| Popis: | Hereditary breast and ovarian cancer (HBOC) is primarily associated with mutations in the BRCA1/2 genes. However, causal variants in other high, moderate, and low penetrance genes proportionally increase the risk of breast/ovarian cancer. This study aims to provide data about the mutation spectrum of HBOC-associated genes in Slovak HBOC families and estimate the ratio of BRCA versus non-BRCA causal variants. We used panel sequencing containing 22 high/moderate-risk susceptibility genes and parallel MLPA analysis of BRCA1/2, CHEK2 genes, to analyze 94 individuals with a strong family/personal history of breast and/or ovarian cancer. The analyzed group consisted of 80 patients diagnosed with cancer (85.1%) and 14 healthy individuals (14.9%) with a positive family history of HBOC syndrome. In total, we have identified 22 causal DNA variants (23.4%) showing 15 primary findings in BRCA1/2 genes (68.2%) and 7 positive secondary findings in CHEK2, PALB2, CDH1, and MUTYH genes (31.8%). The most frequent pathogenic alterations were BRCA1 mutations c.181T>G and CNV variant (c.5573-?_c.5701+?)del, known as deletion of exons 21-22. Besides known mutations, the BRCA1 variant c.2794del (p.Val932Leufs*68) and variant c.2480dup (p.Tyr827*) in the CDH1 gene represent the novel, previously unpublished variants that might be population-specific. In conclusion, we provide the first report of multigene panel testing in Slovak HBOC families demonstrating that almost one-third of pathogenic mutations are situated in susceptibility genes other than BRCA1/2. Although multigene panel testing requires precise data filtration and interpretation, it might bring the relevant data for clinical management of the patients. |
| Databáze: | OpenAIRE |
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