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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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 [12, 13, 14] ; Maximo, Valdemar [1, 2, 12] ; Soares, Paula [1, 2, 12] ; Sobrinho-Simoes, Manuel [1, 2, 12, 11] ; Reis, Rui Manuel [8, 9, 3] ; Lima, Jorge [1, 2, 12]
Total Authors: 23
Affiliation:
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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] Univ Porto, Fac Med, Rua Campo Alegre 823, P-4100 Oporto - Portugal
[13] Ctr Hosp S Joao, Dept Neurosurg, Oporto - Portugal
[14] CUF Hosp, Neurosci Dept, Oporto - Portugal
Total Affiliations: 14
Document type: Journal article
Source: International Journal of Cancer; v. 139, n. 2, p. 414-423, JUL 15 2016.
Web of Science Citations: 19
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. 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)

FAPESP's process: 12/19590-0 - Mutational profile of glioblastoma primary cultures
Grantee:Rui Manuel Vieira Reis
Support type: Regular Research Grants
FAPESP's process: 13/25787-3 - Study of biomarkers of prognosis and response to therapy in gastrointestinal stromal tumors (GISTs)
Grantee:Nathália Cristina Campanella
Support type: Scholarships in Brazil - Doctorate (Direct)