Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer

• Published in: Scientific reports Vol. 7; no. 1; p. 37984
• Main Authors: Feliubadaló, Lídia, Tonda, Raúl, Gausachs, Mireia, Trotta, Jean-Rémi, Castellanos, Elisabeth, López-Doriga, Adriana, Teulé, Àlex, Tornero, Eva, Del Valle, Jesús, Gel, Bernat, Gut, Marta, Pineda, Marta, González, Sara, Menéndez, Mireia, Navarro, Matilde, Capellá, Gabriel, Gut, Ivo, Serra, Eduard, Brunet, Joan, Beltran, Sergi, Lázaro, Conxi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 04.01.2017
• Subjects: Benchmarking; Cancer; Cribratge genètic; Càncer; Diagnosis; Diagnòstic; Genetic diseases; Genetic Predisposition to Disease; Genetic screening; Genetic Testing - methods; High-Throughput Nucleotide Sequencing; Humans; Malalties hereditàries; MSH2 protein; MSH6 protein; Mutation; Neoplastic Syndromes, Hereditary - diagnosis; Neoplastic Syndromes, Hereditary - genetics; Whole Exome Sequencing - methods
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep37984

Next generation sequencing panels have been developed for hereditary cancer, although there is some debate about their cost-effectiveness compared to exome sequencing. The performance of two panels is compared to exome sequencing. Twenty-four patients were selected: ten with identified mutations (control set) and fourteen suspicious of hereditary cancer but with no mutation (discovery set). TruSight Cancer (94 genes) and a custom panel (122 genes) were assessed alongside exome sequencing. Eighty-three genes were targeted by the two panels and exome sequencing. More than 99% of bases had a read depth of over 30x in the panels, whereas exome sequencing covered 94%. Variant calling with standard settings identified the 10 mutations in the control set, with the exception of MSH6 c.255dupC using TruSight Cancer. In the discovery set, 240 unique non-silent coding and canonic splice-site variants were identified in the panel genes, 7 of them putatively pathogenic (in ATM, BARD1, CHEK2, ERCC3, FANCL, FANCM, MSH2). The three approaches identified a similar number of variants in the shared genes. Exomes were more expensive than panels but provided additional data. In terms of cost and depth, panels are a suitable option for genetic diagnostics, although exomes also identify variants in non-targeted genes.