title: The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism.
abstract: 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.
authors.affiliation: Cancer Signaling and Metabolism Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Batista
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cruvinel-Carloni
authors.affiliation: Cancer Signaling and Metabolism Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.|Institute of Biomedical Sciences of Abel Salazar, University of Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Vinagre
authors.affiliation: Cancer Signaling and Metabolism Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Peixoto
authors.affiliation: Cancer Signaling and Metabolism Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
authors.forename: Telmo A
authors.initials: TA
authors.lastname: Catarino
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
authors.forename: Nathalia Cristina
authors.initials: NC
authors.lastname: Campanella
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.
authors.forename: Weder
authors.initials: W
authors.lastname: Menezes
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.|Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: Aline Paixão
authors.initials: AP
authors.lastname: Becker
authors.affiliation: Department of Pathology, Barretos Cancer Hospital, São Paulo, Brazil.
authors.forename: Gisele Caravina
authors.initials: GC
authors.lastname: de Almeida
authors.affiliation: Department of Pathology, Barretos Cancer Hospital, São Paulo, Brazil.
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Matsushita
authors.affiliation: Department of Neurosurgery, Barretos Cancer Hospital, São Paulo, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Clara
authors.affiliation: Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: Luciano
authors.initials: L
authors.lastname: Neder
authors.affiliation: Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Viana-Pereira
authors.affiliation: Department of Pathology, Hospital Pedro Hispano, Matosinhos, Portugal.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Honavar
authors.affiliation: Department of Pathology, Centro Hospitalar de S. João, Porto, Portugal.
authors.forename: Lígia
authors.initials: L
authors.lastname: Castro
authors.affiliation: Department of Pathology, Centro Hospitalar de S. João, Porto, Portugal.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Lopes
authors.affiliation: Department of Neurosurgery, Centro Hospitalar de S. João, Porto, Portugal.|Medical Faculty of the University of Porto, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Carvalho
authors.affiliation: Department of Neurosurgery, Centro Hospitalar de S. João, Porto, Portugal.|Medical Faculty of the University of Porto, Portugal.|Neurosciences Department, CUF Hospital, Porto, Portugal.
authors.forename: Rui Manuel
authors.initials: RM
authors.lastname: Vaz
authors.affiliation: Cancer Signaling and Metabolism Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.|Medical Faculty of the University of Porto, Portugal.
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.affiliation: Cancer Signaling and Metabolism Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.|Medical Faculty of the University of Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.affiliation: Cancer Signaling and Metabolism Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.|Department of Pathology, Centro Hospitalar de S. João, Porto, Portugal.|Medical Faculty of the University of Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.|Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Rui Manuel
authors.initials: RM
authors.lastname: Reis
authors.affiliation: Cancer Signaling and Metabolism Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.|Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.|Medical Faculty of the University of Porto, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Lima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*; D055815:Young Adult
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: TERT SNP; TERT promoter mutations; glioblastoma; prognosis; survival