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dc.contributor.authorSayagués, José María-
dc.contributor.authorCarmen, Sofía del-
dc.contributor.authorAbad, María del Mar-
dc.contributor.authorCorchete, Luis A.-
dc.contributor.authorBengoechea, Óscar-
dc.contributor.authorAnduaga, María Fernanda-
dc.contributor.authorBaldeón, María Jesús-
dc.contributor.authorCruz, Juan Jesús-
dc.contributor.authorAlcazar, Jose Antonio-
dc.contributor.authorAngoso, María-
dc.contributor.authorGonzález, Marcos-
dc.contributor.authorGarcía, Jacinto-
dc.contributor.authorMuñoz-Bellvis, Luís-
dc.contributor.authorOrfao, Alberto-
dc.contributor.authorSarasquete, María Eugenia-
dc.date.accessioned2018-08-31T12:09:34Z-
dc.date.available2018-08-31T12:09:34Z-
dc.date.issued2018-
dc.identifierdoi: 10.18632/oncotarget.25300-
dc.identifiere-issn: 1949-2553-
dc.identifier.citationOncotarget 9(35): 24081-24096 (2018)-
dc.identifier.urihttp://hdl.handle.net/10261/169320-
dc.description.abstractThe prognostic impact of KRAS mutations and other KRAS-related and nonrelated genes such as BRAF, NRAS and TP53, on sporadic colorectal cancer (sCRC) remain controversial and/or have not been fully established. Here we investigated the frequency of such mutations in primary sCRC tumors and their impact on patient progression-free survival (PFS) and overall survival (OS). Primary tumor tissues from 87 sCRC patients were analysed using a custom-built next generation sequencing (NGS) panel to assess the hotspot mutated regions of KRAS/NRAS (exons 2, 3 and 4), BRAF (exon 15) and TP53 (all exons). Overall, mutations in these genes were detected in 46/87 sCRC tumors analyzed (53%) with the following frequencies per gene: TP53, 33%; KRAS, 28%; BRAF, 7%; and NRAS, 1%. A significant association was found between KRAS mutations and right side colon tumor location (p=0.05), well-differentiated tumors (p=0.04) and absence of lymphovascular invasion (p=0.05). In turn, BRAF-mutated tumors frequently corresponded to poorlyor moderately-differentiated sCRC (p=0.02) and showed a higher frequency of peritoneal carcinomatosis (p=0.006) and microsatellite instability (p=0.007). From the prognostic point of view, the BRAF mutational status together with the TNM stage were the only variables that showed an independent adverse impact on patient outcome in the multivariate analyses for both PFS and OS. Based on these results a scoring system was built and patients were classified into three prognostic subgroups with different PFS rates at 2 years: 91% vs. 77% vs. 0%, respectively (p < 0.0001). Additional prospective studies in larger series of sCRC patients where mutations in genes other than those investigated here are required to validate the utility of the proposed predictive model.-
dc.description.sponsorshipThis work has been partially supported by grants from the Instituto de Salud Carlos III (ISCIII; Ministerio de Sanidad y Consumo, Madrid, Spain) (PI12/02053-FIS), Gerencia Regional de Salud de Castilla y León, Valladolid, Spain (GRS1302/A/16), Consejería de Sanidad (Junta de Castilla y León, Valladolid, Spain) (BIO/SA46/14, BIO/SA02/13), RTICC from the ISCIII (RD12/0020/0035-FEDER, RD12/0036/0048-FEDER) and CIBERONC (CB16/12/00400 and CB16/12/00233), Fundación Memoria de Don Samuel Solórzano Barruso, (Salamanca, Spain) and Fundación Eugenio Rodríguez Pascual, (Madrid, Spain). JM Sayagués and ME Sarasquete are supported by grants (CES11/004 and CP13/00080) from the ISCIII, Ministerio de Ciencia e Innovación, Madrid, Spain.-
dc.publisherImpact Journals-
dc.relation.isversionofPublisher's version-
dc.rightsopenAccess-
dc.subjectAnti-EGFR therapy-
dc.subjectColorectal cancer-
dc.subjectPrognosis-
dc.subjectBRAF V600E mutation-
dc.titleCombined assessment of the TNM stage and BRAF mutational status at diagnosis in sporadic colorectal cancer patients-
dc.typeartículo-
dc.relation.publisherversionhttps://doi.org/10.18632/oncotarget.25300-
dc.date.updated2018-08-31T12:09:34Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.rights.licensehttp://creativecommons.org/licenses/by/3.0/-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderFundación Eugenio Rodríguez Pascual-
dc.contributor.funderFundación Memoria de D. Samuel Solorzano Barruso-
dc.contributor.funderRed Temática de Investigación Cooperativa en Cáncer (España)-
dc.contributor.funderJunta de Castilla y León-
dc.contributor.funderMinisterio de Sanidad y Consumo (España)-
dc.contributor.funderInstituto de Salud Carlos III-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100008055es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
dc.identifier.pmid29844874-
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