Exploring hTERT promoter methylation in cutaneous T‐cell lymphomas

Autor: Alain Chebly, Joana Ropio, Jean‐Marie Peloponese, Sandrine Poglio, Martina Prochazkova‐Carlotti, Floriane Cherrier, Jacky Ferrer, Yamina Idrissi, Evelyne Segal‐Bendirdjian, Eliane Chouery, Chantal Farra, Anne Pham‐Ledard, Marie Beylot‐Barry, Jean‐Philippe Merlio, Roland Tomb, Edith Chevret
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecular Oncology, Vol 16, Iss 9, Pp 1931-1946 (2022)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
12377422
DOI: 10.1002/1878-0261.12946
Popis: Cutaneous T‐cell lymphomas (CTCLs) are telomerase‐positive tumors expressing hTERT, although neither gene rearrangement/amplification nor promoter hotspot mutations could explain the hTERT re‐expression. As the hTERT promoter is rich in CpG, we investigated the contribution of epigenetic mechanisms in its re‐expression. We analyzed hTERT promoter methylation status in CTCL cells compared with healthy cells. Gene‐specific methylation analyses revealed a common methylation pattern exclusively in tumor cells. This methylation pattern encompassed a hypermethylated distal region from −650 to −150 bp and a hypomethylated proximal region from −150 to +150 bp. Interestingly, the hypermethylated region matches with the recently named TERT hypermethylated oncogenic region (THOR). THOR has been associated with telomerase reactivation in many cancers, but it has so far not been reported in cutaneous lymphomas. Additionally, we assessed the effect of THOR on two histone deacetylase inhibitors (HDACi), romidepsin and vorinostat, both approved for CTCL treatment and a DNA methyltransferase inhibitor (DNMTi) 5‐azacytidine, unapproved for CTCL. Contrary to our expectations, the findings reported herein revealed that THOR methylation is relatively stable under these epigenetic drugs' pressure, whereas these drugs reduced the hTERT gene expression.
Databáze: Directory of Open Access Journals
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