Telomerase promoter mutations in cancer: an emerging molecular biomarker?

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 rea...

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Bibliographic Details
Published in:Virchows Archiv : an international journal of pathology 2014-08, Vol.465 (2), p.119-133
Main Authors: Vinagre, João, Pinto, Vasco, Celestino, Ricardo, Reis, Marta, Pópulo, Helena, Boaventura, Paula, Melo, Miguel, Catarino, Telmo, Lima, Jorge, Lopes, José Manuel, Máximo, Valdemar, Sobrinho-Simões, Manuel, Soares, Paula
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - genetics
Humans
Medicine
Medicine & Public Health
Molecular Biology - methods
Mutation
Neoplasms - diagnosis
Neoplasms - genetics
Neoplasms - mortality
Pathology
Prognosis
Promoter Regions, Genetic
Review and Perspectives
Survival Rate
Telomerase - genetics
Telomere - physiology
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Summary: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.
ISSN:0945-6317
1432-2307
DOI:10.1007/s00428-014-1608-4