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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism

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Autor(es):
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Batista, Rui [1, 2] ; Cruvinel-Carloni, Adriana [3] ; Vinagre, Joao [1, 2, 4] ; Peixoto, Joana [1, 2] ; Catarino, Telmo A. [1, 2] ; Campanella, Nathalia Cristina [3] ; Menezes, Weder [3] ; Becker, Aline Paixao [5, 3] ; de Almeida, Gisele Caravina [6] ; Matsushita, Marcus M. [6] ; Clara, Carlos [7] ; Neder, Luciano [5] ; Viana-Pereira, Marta [8, 9] ; Honavar, Mrinalini [10] ; Castro, L. Igia [11] ; Lopes, Jose Manuel [11] ; Carvalho, Bruno [12, 13] ; Vaz, Rui Manuel [13, 12, 14] ; Maximo, Valdemar [1, 2, 13] ; Soares, Paula [1, 2, 13] ; Sobrinho-Simoes, Manuel [1, 2, 13, 11] ; Reis, Rui Manuel [8, 9, 3] ; Lima, Jorge [1, 2, 13]
Número total de Autores: 23
Afiliação do(s) autor(es):
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[1] Univ Porto, Canc Signaling & Metab Grp, Inst Invest & Inovacao Saude, Rua Campo Alegre 823, P-4100 Oporto - Portugal
[2] Univ Porto IPATIMUP, Canc Signaling & Metab Grp, Inst Mol Pathol & Immunol, Oporto - Portugal
[3] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo - Brazil
[4] Univ Porto, Inst Biomed Sci Abel Salazar, Rua Campo Alegre 823, P-4100 Oporto - Portugal
[5] Univ Sao Paulo, Ribeirao Preto Sch Med, Sao Paulo - Brazil
[6] Barretos Canc Hosp, Dept Pathol, Sao Paulo - Brazil
[7] Barretos Canc Hosp, Dept Neurosurg, Sao Paulo - Brazil
[8] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga - Portugal
[9] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal
[10] Hosp Pedro Hispano, Dept Pathol, Matosinhos - Portugal
[11] Ctr Hosp S Joao, Dept Pathol, Oporto - Portugal
[12] Ctr Hosp S Joao, Dept Neurosurg, Oporto - Portugal
[13] Univ Porto, Fac Med, Rua Campo Alegre 823, P-4100 Oporto - Portugal
[14] CUF Hosp, Neurosci Dept, Oporto - Portugal
Número total de Afiliações: 14
Tipo de documento: Artigo Científico
Fonte: International Journal of Cancer; v. 139, n. 2, p. 414-423, JUL 15 2016.
Citações Web of Science: 19
Resumo

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. (AU)

Processo FAPESP: 12/19590-0 - Perfil mutacional de linhagens primárias de glioblastomas
Beneficiário:Rui Manuel Vieira Reis
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/25787-3 - Estudo de biomarcadores de prognóstico e resposta terapêutica em tumores estromais gastrointestinais (GISTs)
Beneficiário:Nathália Cristina Campanella
Linha de fomento: Bolsas no Brasil - Doutorado Direto