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Integrated analysis of germline and tumor DNA identifies new candidate genes involved in familial colorectal cancer

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dc.contributor.author Díaz-Gay, Marcos
dc.contributor.author Park, Solip
dc.contributor.author Parra Farré, Genís
dc.contributor.author Laurie, Steven, 1973-
dc.contributor.author Beltran, Sergi
dc.contributor.author Castellví Bel, Sergi
dc.date.accessioned 2019-05-21T07:49:38Z
dc.date.available 2019-05-21T07:49:38Z
dc.date.issued 2019
dc.identifier.citation Díaz-Gay M, Franch-Expósito S, Arnau-Collell C, Park S, Supek F, Muñoz J et al. Integrated analysis of germline and tumor DNA identifies new candidate genes involved in familial colorectal cancer. Cancers (Basel). 2019; 11(3). pii: E362. DOI 10.3390/cancers11030362
dc.identifier.issn 2072-6694
dc.identifier.uri http://hdl.handle.net/10230/37252
dc.description.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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartof Cancers (Basel). 2019; 11(3). pii: E362
dc.rights © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Integrated analysis of germline and tumor DNA identifies new candidate genes involved in familial colorectal cancer
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3390/cancers11030362
dc.subject.keyword Colorectal cancer
dc.subject.keyword Whole-exome sequencing
dc.subject.keyword Predisposition to disease
dc.subject.keyword Germline–tumor analysis
dc.subject.keyword Mutational signatures
dc.subject.keyword Computational genomics
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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