title: Telomerase promoter mutations in cancer: an emerging molecular biomarker?
abstract: Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the "alternative mechanism of telomere lengthening" (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target.
authors.affiliation: Institute of Molecular Pathology and Immunology of University of Porto (IPATIMUP), 4200-465, Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Vinagre
authors.forename: Vasco
authors.initials: V
authors.lastname: Pinto
authors.forename: Ricardo
authors.initials: R
authors.lastname: Celestino
authors.forename: Marta
authors.initials: M
authors.lastname: Reis
authors.forename: Helena
authors.initials: H
authors.lastname: Pópulo
authors.forename: Paula
authors.initials: P
authors.lastname: Boaventura
authors.forename: Miguel
authors.initials: M
authors.lastname: Melo
authors.forename: Telmo
authors.initials: T
authors.lastname: Catarino
authors.forename: Jorge
authors.initials: J
authors.lastname: Lima
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Lopes
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D006801:Humans; D008967:Molecular Biology / Q000379:methods; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D011401:Promoter Regions, Genetic; D015996:Survival Rate; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase