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Nat Rev Gastroenterol Hepatol. 2019 Jun 28. doi: 10.1038/s41575-019-0165-3. [Epub ahead of print]

The role of telomeres and telomerase in cirrhosis and liver cancer.

Author information

1
Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, USPC, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France. naultjc@gmail.com.
2
Liver unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France. naultjc@gmail.com.
3
Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France. naultjc@gmail.com.
4
Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, USPC, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France.
5
Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, USPC, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France. jessica.zucman-rossi@inserm.fr.
6
Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France. jessica.zucman-rossi@inserm.fr.

Abstract

Telomerase is a key enzyme for cell survival that prevents telomere shortening and the subsequent cellular senescence that is observed after many rounds of cell division. In contrast, inactivation of telomerase is observed in most cells of the adult liver. Absence of telomerase activity and shortening of telomeres has been implicated in hepatocyte senescence and the development of cirrhosis, a chronic liver disease that can lead to hepatocellular carcinoma (HCC) development. During hepatocarcinogenesis, telomerase reactivation is required to enable the uncontrolled cell proliferation that leads to malignant transformation and HCC development. Part of the telomerase complex, telomerase reverse transcriptase, is encoded by TERT, and several mechanisms of telomerase reactivation have been described in HCC that include somatic TERT promoter mutations, TERT amplification, TERT translocation and viral insertion into the TERT gene. An understanding of the role of telomeres and telomerase in HCC development is important to develop future targeted therapies and improve survival of this disease. In this Review, the roles of telomeres and telomerase in liver carcinogenesis are discussed, in addition to their potential translation to clinical practice as biomarkers and therapeutic targets.

PMID:
31253940
DOI:
10.1038/s41575-019-0165-3

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