title: Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer.
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.
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Lídia
authors.initials: L
authors.lastname: Feliubadaló
authors.affiliation: Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Tonda
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Gausachs
authors.affiliation: Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors.forename: Jean-Rémi
authors.initials: JR
authors.lastname: Trotta
authors.affiliation: Genetic Variation in Cancer Group, Joint Program on Hereditary Cancer, Institut de Medicina Predictiva i Personalitzada del Càncer, Badalona, Catalonia, Spain.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Castellanos
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: López-Doriga
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Àlex
authors.initials: À
authors.lastname: Teulé
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Tornero
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Del Valle
authors.affiliation: Genetic Variation in Cancer Group, Joint Program on Hereditary Cancer, Institut de Medicina Predictiva i Personalitzada del Càncer, Badalona, Catalonia, Spain.
authors.forename: Bernat
authors.initials: B
authors.lastname: Gel
authors.affiliation: Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gut
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pineda
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: González
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Menéndez
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Navarro
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellá
authors.affiliation: Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.affiliation: Genetic Variation in Cancer Group, Joint Program on Hereditary Cancer, Institut de Medicina Predictiva i Personalitzada del Càncer, Badalona, Catalonia, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Serra
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IdibGi in Girona, Catalonia, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Brunet
authors.affiliation: Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Beltran
authors.affiliation: Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, IDIBELL campus in Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Conxi
authors.initials: C
authors.lastname: Lázaro
mesh_terms: D019985:Benchmarking; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis* / Q000235:genetics; D000073359:Exome Sequencing / Q000379:methods