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

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 (co...

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Published in:Scientific reports 2017-01
Main Authors: Feliubadaló i Elorza, Maria Lídia, Tonda, Raúl, Gausachs, Mireia, Trotta, Jean Rémi, Castellanos, Elisabeth, López Dóriga Guerra, Adriana, Teulé-Vega, Àlex, Tornero, Eva, Valle, Jesús del, Gel, Bernat, Gut, Marta, Pineda Riu, Marta, González, Sara, Menéndez Vilà, Mireia, Navarro, Matilde, Capellá, G. (Gabriel), Gut, Ivo, Serra, Eduard, Brunet, Joan, Beltran, Sergi, Lázaro García, Conxi
Format: Article
Language:English
Subjects:
Cancer
Cribratge genètic
Càncer
Diagnosis
Diagnòstic
Genetic diseases
Genetic screening
Malalties hereditàries
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Summary: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. Eightythree 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.
ISSN:2045-2322
2045-2322