Author(s):
Batista, Rui ; Cruvinel-Carloni, Adriana ; Vinagre, João ; Peixoto, Joana ; Catarino, Telmo A. ; Campanella, Nathalia Cristina ; Menezes, Weder ; Becker, Aline Paixão ; Pereira, Marta Sofia Carvalho Ribeiro Viana ; Reis, R. M. ; Soares, Ana Paula
Date: 2016
Persistent ID: http://hdl.handle.net/1822/45101
Origin: RepositóriUM - Universidade do Minho
Project/scholarship:
info:eu-repo/grantAgreement/FCT/5876-PPCDTI/115513/PT
;
info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F81940%2F2011/PT;
Subject(s): TERT promoter mutations; Glioblastoma; Prognosis; Survival; TERT SNP; Science & Technology; Ciências Médicas::Medicina Básica
Description
Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Several studies have shown that TERTp mutations are associated with clinicopathological features; in some instances, TERTp mutations were considered as biomarkers of poor prognosis. The rs2853669 SNP, located in the TERT promoter region, was reported to modulate the increased TERT expression levels induced by the recurrent somatic mutations. In this study we aimed to determine the frequency and prognostic value of TERTp mutations and TERT rs2853669 SNP in 504 gliomas from Portuguese and Brazilian patients. TERTp mutations were detected in 47.8% of gliomas (216/452). Glioblastomas (GBM) exhibited the highest frequency of TERTp mutations (66.9%); in this glioma subtype, we found a significant association between TERTp mutations and poor prognosis, regardless of the population. Moreover, in a multivariate analysis, TERTp mutations were the only independent prognostic factor. Our data also showed that the poor prognosis conferred by TERTp mutations was restricted to GBM patients carrying the rs2853669 A allele and not in those carrying the G allele. In conclusion, the presence of TERTp mutations was associated with worse prognosis in GBM patients, although such association depended on the status of the rs2853669 SNP. The status of the rs2853669 SNP should be taken in consideration when assessing the prognostic value of TERTp mutations in GBM patients. TERTp mutations and the rs2853669 SNP can be used in the future as biomarkers of glioma prognosis. What's new? Cancer cells avoid senescence in part by reactivating telomerase (TERT), a ribonucleoprotein that replenishes shortening telomeres. Here, the authors discover a positive association between TERT promoter mutations and unfavorable prognosis in glioblastoma patients from Portuguese and Brazilian origin. This association was only observed in patients with a specific allelic background (AA) in a TERT polymorphism (rs2853669) recently linked to enhanced TERT mRNA levels. The authors recommend considering the allelic status of rs2853669 when assessing the prognostic value of TERT promoter mutations in glioblastoma patients.
Portuguese Fundação para a Ciência e Tecnologia and Fundo Europeu de Desenvolvimento Regional (FEDER) and COMPETE – Programa Operacional Factores de Competitividade (POFC); Grant number: PTDC/SAU-ONC/115513/2009; Grant sponsor: Brazilian FAPESP; Grant number: 2012/19590–0; Grant sponsor: Programa Operacional Regional do Norte (ON.2 – O Novo Norte), under Quadro de Referência Estrategico Nacional (QREN) through Fundo Europeu de Desenvolvimento Regional (FEDER); Grant number: Microenvironment, Metabolism and Cancer; Grant sponsor: Fundação para a Ciência e Tecnologia; Grant number: SFRH/BD/81940/2011; Grant sponsor: Fundação para a Ciência e Tecnologia; Grant number: Program Ciência 2007; Grant sponsor: Fundação para a Ciência e Tecnologia; Grant number: Program Ciência 2008; Grant sponsor: Brazilian FAPESP; Grant number: 2013/25787-3; Grant sponsor: NORTE2020; Grant number: NORTE-01-0145-FEDER-000029
Fundação para a Ciência e Tecnologia
info:eu-repo/semantics/publishedVersion
