RT info:eu-repo/semantics/article
T1 A comprehensive custom panel evaluation for routine hereditary cancer testing: improving the yield of germline mutation detection
A1 Velázquez, Carolina
A1 Lastra, Enrique
A1 Avila Cobos, Francisco
A1 Abella, Luis
A1 de la Cruz, Virginia
A1 Hernando, Blanca Ascensión
A1 Hernández, Lara
A1 Martínez, Noemí
A1 Infante, Mar
A1 Durán, Mercedes
AB BackgroundIn the context of our Regional Program of Hereditary Cancer, individuals fulfilling the criteria are tested for germline mutations to subsequently establish the clinical management. Our standard diagnostic approach focuses on sequencing a few classic high-risk genes, a method that frequently renders uninformative genetic results. This study aims to examine the improved yield offered by an On-Demand panel.MethodsWe designed an On-Demand panel for the analysis of 35-genes associated with inherited cancer susceptibility in a total of 128 cases of Hereditary Breast and Ovarian Cancer (HBOC) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC).ResultsEighteen deleterious mutations were detected, in both routinely (BRCA2, MLH1, MSH2, PMS2) and non-routinely (ATM, BLM, BRIP1, CHEK2, MUTYH) tested genes. The screening extended to 35 genes rendered by patients carrying several- up to 6-Variants of Unknown Significance (VUS). Moreover, we confirmed the splicing disruption at RNA level for a not previously reported BRIP1 splicing mutation. Using an On-Demand panel, we identified 18 pathogenic mutation carriers, seven of which would have gone unnoticed with traditional analysis.ConclusionsOur results reinforce the utility of NGS gene panels in the diagnostic routine to increase the performance of genetic testing, especially in individuals from families with overlapping cancer phenotypes.
PB BMC Springer Nature
YR 2020
FD 2020
LK https://uvadoc.uva.es/handle/10324/73285
UL https://uvadoc.uva.es/handle/10324/73285
LA spa
NO Journal of Translational Medicine (2020) 18:232
DS UVaDOC
RD 31-ene-2025