Show simple item record

dc.contributor.authorDíaz Gay, Marcos
dc.contributor.authorFranch Expósito, Sebastià
dc.contributor.authorArnau Collell, Coral
dc.contributor.authorPark, Solip
dc.contributor.authorSupek, Fran
dc.contributor.authorMuñoz, Jenifer
dc.contributor.authorBonjoch, Laia
dc.contributor.authorGratacós Mulleras, Anna
dc.contributor.authorSánchez Rojas, Paula A.
dc.contributor.authorEsteban-Jurado, Clara
dc.contributor.authorOcaña, Teresa
dc.contributor.authorCuatrecasas, Miriam
dc.contributor.authorVila Casadesús, Maria
dc.contributor.authorLozano, Juan José
dc.contributor.authorParra, Genis
dc.contributor.authorLaurie, Steve
dc.contributor.authorBeltran, Sergi
dc.contributor.authorEPICOLON Consortium
dc.contributor.authorCastells, Antoni
dc.contributor.authorBujanda Fernández de Pierola, Luis
dc.contributor.authorCubiella, Joaquín
dc.contributor.authorBalaguer, Francesc
dc.contributor.authorCastellví-Bel, Sergi
dc.date.accessioned2019-05-09T08:13:49Z
dc.date.available2019-05-09T08:13:49Z
dc.date.issued2019-03-13
dc.identifier.citationCancers 11(3) : (2019) // Article ID 362es_ES
dc.identifier.issn2072-6694
dc.identifier.urihttp://hdl.handle.net/10810/32710
dc.description.abstractColorectal 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.es_ES
dc.description.sponsorshipM.D.-G. was supported by a contract from Agència de Gestió d’Ajuts Universitaris i de Recerca -AGAUR- (Generalitat de Catalunya, 2018FI_B1_00213). S.F.-E., J.M., C.A.-C., C.E.-J. and J.J.L. were supported by a contract from CIBEREHD. CIBEREHD is funded by the Instituto de Salud Carlos III. This research was supported by grants from Fondo de Investigación Sanitaria/FEDER (17/00878), Fundación Científica de la Asociación Española contra el Cáncer (GCB13131592CAST), PERIS (SLT002/16/00398, Generalitat de Catalunya), CERCA Programme (Generalitat de Catalunya) and Agència de Gestió d’Ajuts Universitaris i de Recerca (Generalitat de Catalunya, GRPRE 2017SGR21, GRC 2017SGR653). This article is based upon work from COST Action CA17118, supported by COST (European Cooperation in Science and Technology)es_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectcolorectal canceres_ES
dc.subjectcomputational genomicses_ES
dc.subjectgermline-tumor analysises_ES
dc.subjectmutational signatureses_ES
dc.subjectpredisposition to diseasees_ES
dc.subjectwhole-exome sequencinges_ES
dc.titleIntegrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Canceres_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holderThis is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).es_ES
dc.rights.holderAtribución 3.0 España*
dc.relation.publisherversionhttps://www.mdpi.com/2072-6694/11/3/362es_ES
dc.identifier.doi10.3390/cancers11030362
dc.departamentoesMedicinaes_ES
dc.departamentoeuMedikuntzaes_ES


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
Except where otherwise noted, this item's license is described as This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).