Titre
Intron 4-5 hTERT DNA Hypermethylation in Merkel Cell Carcinoma: Frequency, Association with Other Clinico-pathological Features and Prognostic Relevance.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Ricci, C.
Auteure/Auteur
Morandi, L.
Auteure/Auteur
Ambrosi, F.
Auteure/Auteur
Righi, A.
Auteure/Auteur
Gibertoni, D.
Auteure/Auteur
Maletta, F.
Auteure/Auteur
Agostinelli, C.
Auteure/Auteur
Corradini, A.G.
Auteure/Auteur
Uccella, S.
Auteure/Auteur
Asioli, S.
Auteure/Auteur
Sessa, F.
Auteure/Auteur
La Rosa, S.
Auteure/Auteur
Papotti, M.G.
Auteure/Auteur
Asioli, S.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1559-0097
Statut éditorial
Publié
Date de publication
2021-09
Volume
32
Numéro
3
Première page
385
Dernière page/numéro d’article
395
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
PID Serval
serval:BIB_1FA0D2B729F8
PMID
Open Access
Oui
Date de création
2021-04-30T08:14:21.434Z
Date de création dans IRIS
2025-05-20T15:48:16Z
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Nom
33909215.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
1.23 MB
Format
Adobe PDF
PID Serval
serval:BIB_1FA0D2B729F8.P001
URN
urn:nbn:ch:serval-BIB_1FA0D2B729F87
Somme de contrôle
(MD5):bc6e2f861f6d4b3d45dd233a251ddb8c