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Frequency of TERT promoter mutations in human cancers

2013; Nature Portfolio; Volume: 4; Issue: 1 Linguagem: Inglês

10.1038/ncomms3185

2041-1723

João Vinagre, Ana Paula de Almeida, Helena Pópulo, Rui Batısta, Joana Lyra, Vasco Pinto, Ricardo Coelho, Ricardo Celestino, Hugo Prazeres, Luís Lima, Miguel Melo, Adriana Gaspar da Rocha, Ana Preto, Patrícia Castro, Lígia Castro, Fernando Pardal, José Manuel Lopes, Lúcio Lara Santos, Rui Manuel Reis, José Cameselle-Teijeiro, Manuel Sobrinho‐Simões, Jorge Lima, Valdemar Máximo, Paula Soares,

Hedgehog Signaling Pathway Studies

Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase. Reactivation of telomerase has been implicated in human tumorigenesis. Here, somatic mutations in the TERT promoter are reported in cancers of the central nervous system, bladder, follicular cell-derived thyroid and melanoma, thus demonstrating that TERTpromoter mutations are a frequent event in human cancer.