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Title: Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer
Author: Díaz Gay, Marcos
Franch Expósito, Sebastià
Arnau Collell, Coral
Park, Solip
Supek, Fran
Muñoz, Jenifer
Bonjoch Gassol, Laia
Gratacós Mulleras, Anna
Sánchez Rojas, Paula A.
Esteban Jurado, Clara
Ocaña, Teresa
Cuatrecasas Freixas, Miriam
Vila Casadesús, Maria
Lozano, Juan José
Parra, Genís
Laurie, Steve
Beltrán, Sergi
EPICOLON Consortium
Castells Garangou, Antoni
Bujanda, Luis
Cubiella, Joaquín
Balaguer Prunés, Francesc
Castellví Bel, Sergi
Keywords: Càncer colorectal
Colorectal cancer
Issue Date: 13-Mar-2019
Publisher: MDPI
Abstract: Colorectal cancer (CRC) shows aggregation in some families but no alterations in the known hereditary CRC genes. We aimed to identify new candidate genes which are potentially involved in germline predisposition to familial CRC. An integrated analysis of germline and tumor whole-exome sequencing data was performed in 18 unrelated CRC families. Deleterious single nucleotide variants (SNV), short insertions and deletions (indels), copy number variants (CNVs) and loss of heterozygosity (LOH) were assessed as candidates for first germline or second somatic hits. Candidate tumor suppressor genes were selected when alterations were detected in both germline and somatic DNA, fulfilling Knudson's two-hit hypothesis. Somatic mutational profiling and signature analysis were also performed. A series of germline-somatic variant pairs were detected. In all cases, the first hit was presented as a rare SNV/indel, whereas the second hit was either a different SNV (3 genes) or LOH affecting the same gene (141 genes). BRCA2, BLM, ERCC2, RECQL, REV3L and RIF1 were among the most promising candidate genes for germline CRC predisposition. The identification of new candidate genes involved in familial CRC could be achieved by our integrated analysis. Further functional studies and replication in additional cohorts are required to confirm the selected candidates.
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It is part of: Cancers, 2019, vol. 11, num. 3, p. 362
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ISSN: 2072-6694
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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