Benchmarking of whole exome sequencing and ad hoc designed panels for genetic testing of hereditary cancer

Feliubadaló, Lídia; Tonda, Raúl; Trotta, Jean-Remi; Gut, Marta; Gut, Ivo Glynne; Beltran, Sergi; Lázaro García, Conxi

doi:http://dx.doi.org/10.1038/srep37984

Benchmarking of whole exome sequencing and ad hoc designed panels for genetic testing of hereditary cancer

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Feliubadaló L, Tonda R, Gausachs M, Trotta JR, Castellanos E, López-Doriga A, et al. Benchmarking of whole exome sequencing and ad hoc designed panels for genetic testing of hereditary cancer. Sci Rep. 2017 Jan 4;7(1):37984. DOI: 10.1038/srep37984

Abstract

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.