Telomere Maintenance Mechanisms in Cancer

• Published in: Genes Vol. 9; no. 5; p. 241
• Main Authors: Gaspar, Tiago Bordeira, Sá, Ana, Lopes, José Manuel, Sobrinho-Simões, Manuel, Soares, Paula, Vinagre, João
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03-05-2018; MDPI
• Subjects: Cancer; Chromosomes; Genetic transformation; Genomes; Mutation; Review; Telomerase; Telomeres; Tumors; alternative lengthening of telomeres (ALT); telomerase; TERT; TERC; telomere; cancer; promoter; non-defined telomere maintenance mechanism (NDTMM); telomere maintenance mechanism (TMM)
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes9050241

Tumour cells can adopt telomere maintenance mechanisms (TMMs) to avoid telomere shortening, an inevitable process due to successive cell divisions. In most tumour cells, telomere length (TL) is maintained by reactivation of telomerase, while a small part acquires immortality through the telomerase-independent alternative lengthening of telomeres (ALT) mechanism. In the last years, a great amount of data was generated, and different TMMs were reported and explained in detail, benefiting from genome-scale studies of major importance. In this review, we address seven different TMMs in tumour cells: mutations of the
promoter (
), amplification of the genes
and
, polymorphic variants of the
gene and of its promoter, rearrangements of the
gene, epigenetic changes, ALT, and non-defined TMM (NDTMM). We gathered information from over fifty thousand patients reported in 288 papers in the last years. This wide data collection enabled us to portray, by organ/system and histotypes, the prevalence of
mutations,
and
amplifications, and ALT in human tumours. Based on this information, we discuss the putative future clinical impact of the aforementioned mechanisms on the malignant transformation process in different setups, and provide insights for screening, prognosis, and patient management stratification.