dc.contributor.author | Díaz Gay, Marcos | |
dc.contributor.author | Franch Expósito, Sebastià | |
dc.contributor.author | Arnau Collell, Coral | |
dc.contributor.author | Park, Solip | |
dc.contributor.author | Supek, Fran | |
dc.contributor.author | Muñoz, Jenifer | |
dc.contributor.author | Bonjoch, Laia | |
dc.contributor.author | Gratacós Mulleras, Anna | |
dc.contributor.author | Sánchez Rojas, Paula A. | |
dc.contributor.author | Esteban-Jurado, Clara | |
dc.contributor.author | Ocaña, Teresa | |
dc.contributor.author | Cuatrecasas, Miriam | |
dc.contributor.author | Vila Casadesús, Maria | |
dc.contributor.author | Lozano, Juan José | |
dc.contributor.author | Parra, Genis | |
dc.contributor.author | Laurie, Steve | |
dc.contributor.author | Beltran, Sergi | |
dc.contributor.author | EPICOLON Consortium | |
dc.contributor.author | Castells, Antoni | |
dc.contributor.author | Bujanda Fernández de Pierola, Luis | |
dc.contributor.author | Cubiella, Joaquín | |
dc.contributor.author | Balaguer, Francesc | |
dc.contributor.author | Castellví-Bel, Sergi | |
dc.date.accessioned | 2019-05-09T08:13:49Z | |
dc.date.available | 2019-05-09T08:13:49Z | |
dc.date.issued | 2019-03-13 | |
dc.identifier.citation | Cancers 11(3) : (2019) // Article ID 362 | es_ES |
dc.identifier.issn | 2072-6694 | |
dc.identifier.uri | http://hdl.handle.net/10810/32710 | |
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. | es_ES |
dc.description.sponsorship | M.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.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | colorectal cancer | es_ES |
dc.subject | computational genomics | es_ES |
dc.subject | germline-tumor analysis | es_ES |
dc.subject | mutational signatures | es_ES |
dc.subject | predisposition to disease | es_ES |
dc.subject | whole-exome sequencing | es_ES |
dc.title | Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | 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). | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.mdpi.com/2072-6694/11/3/362 | es_ES |
dc.identifier.doi | 10.3390/cancers11030362 | |
dc.departamentoes | Medicina | es_ES |
dc.departamentoeu | Medikuntza | es_ES |