title: Frequency of TERT promoter mutations in human cancers.
abstract: 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.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, 4200-465 Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Vinagre
authors.forename: Ana
authors.initials: A
authors.lastname: Almeida
authors.forename: Helena
authors.initials: H
authors.lastname: Pópulo
authors.forename: Rui
authors.initials: R
authors.lastname: Batista
authors.forename: Joana
authors.initials: J
authors.lastname: Lyra
authors.forename: Vasco
authors.initials: V
authors.lastname: Pinto
authors.forename: Ricardo
authors.initials: R
authors.lastname: Coelho
authors.forename: Ricardo
authors.initials: R
authors.lastname: Celestino
authors.forename: Hugo
authors.initials: H
authors.lastname: Prazeres
authors.forename: Luis
authors.initials: L
authors.lastname: Lima
authors.forename: Miguel
authors.initials: M
authors.lastname: Melo
authors.forename: Adriana Gaspar
authors.initials: AG
authors.lastname: da Rocha
authors.forename: Ana
authors.initials: A
authors.lastname: Preto
authors.forename: Patrícia
authors.initials: P
authors.lastname: Castro
authors.forename: Ligia
authors.initials: L
authors.lastname: Castro
authors.forename: Fernando
authors.initials: F
authors.lastname: Pardal
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Lopes
authors.forename: Lúcio Lara
authors.initials: LL
authors.lastname: Santos
authors.forename: Rui Manuel
authors.initials: RM
authors.lastname: Reis
authors.forename: José
authors.initials: J
authors.lastname: Cameselle-Teijeiro
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.forename: Jorge
authors.initials: J
authors.lastname: Lima
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*
chemical_list: C509186:TERT protein, human; D019098:Telomerase