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Int. J. Mol. Sci. 2018, 19(2), 606; https://doi.org/10.3390/ijms19020606

Telomere Length Maintenance in Cancer: At the Crossroad between Telomerase and Alternative Lengthening of Telomeres (ALT)

Department of Science, Roma Tre University, 00146 Rome, Italy
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Received: 30 December 2017 / Revised: 12 February 2018 / Accepted: 14 February 2018 / Published: 18 February 2018
(This article belongs to the Special Issue Role of Telomeres and Telomerase in Cancer and Aging)
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Abstract

Eukaryotic cells undergo continuous telomere shortening as a consequence of multiple rounds of replications. During tumorigenesis, cells have to acquire telomere DNA maintenance mechanisms (TMMs) in order to counteract telomere shortening, to preserve telomeres from DNA damage repair systems and to avoid telomere-mediated senescence and/or apoptosis. For this reason, telomere maintenance is an essential step in cancer progression. Most human tumors maintain their telomeres expressing telomerase, whereas a lower but significant proportion activates the alternative lengthening of telomeres (ALT) pathway. However, evidence about the coexistence of ALT and telomerase has been found both in vivo in the same cancer populations and in vitro in engineered cellular models, making the distinction between telomerase- and ALT-positive tumors elusive. Indeed, after the development of drugs able to target telomerase, the capability for some cancer cells to escape death, switching from telomerase to ALT, was highlighted. Unfortunately, to date, the mechanism underlying the possible switching or the coexistence of telomerase and ALT within the same cell or populations is not completely understood and different factors could be involved. In recent years, different studies have tried to shed light on the complex regulation network that controls the transition between the two TMMs, suggesting a role for embryonic cancer origin, epigenetic modifications, and specific genes activation—both in vivo and in vitro. In this review, we examine recent findings about the cancer-associated differential activation of the two known TMMs and the possible factors implicated in this process. Furthermore, some studies on cancers are also described that did not display any TMM. View Full-Text
Keywords: cancer; telomere; alternative lengthening of telomeres (ALT); telomerase; cancer therapy cancer; telomere; alternative lengthening of telomeres (ALT); telomerase; cancer therapy
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De Vitis, M.; Berardinelli, F.; Sgura, A. Telomere Length Maintenance in Cancer: At the Crossroad between Telomerase and Alternative Lengthening of Telomeres (ALT). Int. J. Mol. Sci. 2018, 19, 606.

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