Intron 4-5 hTERT DNA Hypermethylation in Merkel Cell Carcinoma: Frequency, Association with Other Clinico-pathological Features and Prognostic Relevance.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_1FA0D2B729F8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intron 4-5 hTERT DNA Hypermethylation in Merkel Cell Carcinoma: Frequency, Association with Other Clinico-pathological Features and Prognostic Relevance.
Journal
Endocrine pathology
Author(s)
Ricci C., Morandi L., Ambrosi F., Righi A., Gibertoni D., Maletta F., Agostinelli C., Corradini A.G., Uccella S., Asioli S., Sessa F., La Rosa S., Papotti M.G., Asioli S.
ISSN
1559-0097 (Electronic)
ISSN-L
1046-3976
Publication state
Published
Issued date
09/2021
Peer-reviewed
Oui
Volume
32
Number
3
Pages
385-395
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Merkel cell carcinoma (MCC) is an aggressive skin tumor with neuroendocrine differentiation, mainly affecting elderly population or immunocompromised individuals. As methylation of the human telomerase reverse transcriptase (mhTERT) has been shown to be a prognostic factor in different tumors, we investigated its role in MCC, in particular in intron 4-5 where rs10069690 has been mapped and recognized as a cancer susceptibility locus. DNA methylation analysis of hTERT gene was assessed retrospectively in a cohort of 69 MCC patients from the University of Bologna, University of Turin and University of Insubria. Overall mortality was evaluated with Kaplan-Meier curves and multivariable Royston-Parmar models. High levels of mhTERT (mhTERT <sub>high</sub> ) (HR = 2.500, p = 0.015) and p63 (HR = 2.659, p = 0.016) were the only two clinico-pathological features significantly associated with a higher overall mortality at the multivariate analysis. We did not find different levels of mhTERT between MCPyV (+) and (-) cases (21 vs 14, p = 0.554); furthermore, mhTERT <sub>high</sub> was strongly associated with older age (80.5 vs 72 years, p = 0.026), no angioinvasion (40.7% vs 71.0%, p = 0.015), lower Ki67 (50 vs 70%, p = 0.005), and PD-L1 expressions in both tumor (0 vs 3%, p = 0.021) and immune cells (0 vs 10%, p = 0.002). mhTERT is a frequently involved epigenetic mechanism and a relevant prognostic factor in MCC. In addition, it belongs to the shared oncogenic pathways of MCC (MCPyV and UV-radiations) and it could be crucial, together with other epigenetic and genetic mechanisms as gene amplification, in determining the final levels of hTERT mRNA and telomerase activity in these patients.
Keywords
HTERT, HTERT intron 4–5, Merkel cell carcinoma, Merkel cell polyomavirus, Methylation, Rs10069690, Telomerase
Pubmed
Web of science
Open Access
Yes
Create date
30/04/2021 10:14
Last modification date
02/09/2021 6:40
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