Carregant...
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/168019
Results of multigene panel testing in familial cancer cases without genetic cause demonstrated by single gene testing
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
We have surveyed 191 prospectively sampled familial cancer patients with no previously detected pathogenic variant in the BRCA1/2, PTEN, TP53 or DNA mismatch repair genes. In all, 138 breast cancer (BC) cases, 34 colorectal cancer (CRC) and 19 multiple early-onset cancers were included. A panel of 44 cancer-predisposing genes identified 5% (9/191) pathogenic or likely pathogenic variants and 87 variants of uncertain significance (VUS). Pathogenic or likely pathogenic variants were identified mostly in familial BC individuals (7/9) and were located in 5 genes: ATM (3), BRCA2 (1), CHEK2 (1), MSH6 (1) and MUTYH (1), followed by multiple early-onset (2/9) individuals, affecting the CHEK2 and ATM genes. Eleven of the 87 VUS were tested, and 4/11 were found to have an impact on splicing by using a minigene splicing assay. We here report for the first time the splicing anomalies using this assay for the variants ATM c.3806A > G and BUB1 c.677C >T, whereas CHEK1 c.61G > A did not result in any detectable splicing anomaly. Our study confirms the presence of pathogenic or likely pathogenic variants in genes that are not routinely tested in the context of the above-mentioned clinical phenotypes. Interestingly, more than half of the pathogenic germline variants were found in the moderately penetrant ATM and CHEK2 genes, where only truncating variants from these genes are recommended to be reported in clinical genetic testing practice.
Matèries
Matèries (anglès)
Citació
Citació
DOMINGUEZ VALENTIN, Mev, NAKKEN, Sigve, TUBEUF, Hélène, VODÁK, Daniel, EKSTROM, Per olaf, NISSEN, Anke m., MORAK, Monika, HOLINSKI-FEDER, Elke, HOLTH, Arild, CAPELLÁ, G. (gabriel), DAVIDSON, Ben, EVANS, D. gareth, MARTINS, Alexandra, MØLLER, Pål, HOVIG, Eivind. Results of multigene panel testing in familial cancer cases without genetic cause demonstrated by single gene testing. _Scientific Reports_. 2019-12-06. Vol. 9. [consulta: 15 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/168019]