English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/63644
logo share SHARE   Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

DC FieldValueLanguage
dc.contributor.authorEstévez-García, Purificación-
dc.contributor.authorCastaño, Ángel-
dc.contributor.authorMartín, Ana C.-
dc.contributor.authorLópez-Ríos, Fernando-
dc.contributor.authorIglesias, Joaquín-
dc.contributor.authorMuñoz-Galván, Sandra-
dc.contributor.authorLópez-Calderero, Iker-
dc.contributor.authorMolina-Pinelo, Sonia-
dc.contributor.authorPastor, María Dolores-
dc.contributor.authorCarnero, Amancio-
dc.contributor.authorPaz-Ares, Luis-
dc.contributor.authorGarcía-Carbonero, Rocío-
dc.identifier.citationBMC Cancer. Nov 12;12(1):514 (2012)-
dc.description.abstractAbstract Background Angiogenesis plays an essential role in tumor growth and metastasis, and is a major target in cancer therapy. VEGFR and PDGFR are key players involved in this process. The purpose of this study was to assess the incidence of genetic variants in these receptors and its potential clinical implications in colorectal cancer (CRC). Methods VEGFR2, PDGFRα and PDGFRβ mutations were evaluated by sequencing their tyrosine kinase domains in 8 CRC cell lines and in 92 samples of patients with CRC. Correlations with clinicopathological features and survival were analyzed. Results Four SNPs were identified, three in PDGFRα [exon 12 (A12): c.1701A>G; exon 13 (A13): c.1809G>A; and exon 17 (A17): c.2439+58C>A] and one in PDGFRβ [exon 19 (B19): c.2601A>G]. SNP B19, identified in 58% of tumor samples and in 4 cell lines (LS174T, LS180, SW48, COLO205), was associated with higher PDGFR and pPDGFR protein levels. Consistent with this observation, 5-year survival was greater for patients with PDGFR B19 wild type tumors (AA) than for those harboring the G-allele genotype (GA or GG) (51% vs 17%; p=0.073). Multivariate analysis confirmed SNP B19 (p=0.029) was a significant prognostic factor for survival, independent of age (p=0.060) or TNM stage (p<0.001). Conclusions PDGFRβ exon 19 c.2601A>G SNP is commonly encountered in CRC patients and is associated with increased pathway activation and poorer survival. Implications regarding its potential influence in response to PDGFR-targeted agents remain to be elucidated.-
dc.description.sponsorshipThis work was supported by a grant of the Ministerio de Ciencia y Tecnologia of Spain (FIT-010000-2006-45). PEG is funded by a Rio Hortega grant (09/00207) from the Instituto de Salud Carlos III (ISCiii), Ministerio de Sanidad, Spain. SMP is funded by the ISCiii (CD1100153), Fundación Científica de la Asociacion Española Contra el Cancer (AECC), Consejeria de Salud – Junta de Andalucia (PI-0224/2009) and Fundacion Mutua Madrileña (2009). MDP is funded by the ISCiii (CD0900148). LPA is funded by the ISCiii (PI081156 and PI1102688), Consejería de Innovacion, Ciencia y Empresa – Junta de Andalucia (P08-CVI-04090) and the 75th Anniversary Roche Spain Fellowship. RGC is funded by the ISCiii (PI 10.02164).-
dc.publisherBioMed Central-
dc.relation.isversionofPublisher’s version-
dc.titlePDGFR / and VEGFR2 polymorphisms in colorectal cancer: incidence and implications in clinical outcome-
dc.description.versionPeer Reviewed-
dc.rights.holderPurificacion Estevez-Garcia et al.; licensee BioMed Central Ltd.-
Appears in Collections:(IBIS) Artículos
Files in This Item:
File Description SizeFormat 
1471-2407-12-514.xml87,41 kBXMLView/Open
1471-2407-12-514.pdf506,97 kBAdobe PDFThumbnail
1471-2407-12-514-S1.DOC70,5 kBMicrosoft WordView/Open
Show simple item record

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.