Infrequent promoter methylation of the MGMT gene in liver metastases from uveal melanoma.

Détails

ID Serval
serval:BIB_4758A939ADF7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Infrequent promoter methylation of the MGMT gene in liver metastases from uveal melanoma.
Périodique
International Journal of Cancer
Auteur(s)
Voelter V., Diserens A.C., Moulin A., Nagel G., Yan P., Migliavacca E., Rimoldi D., Hamou M.F., Kaina B., Leyvraz S., Hegi M.E.
ISSN
1097-0215
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
123
Numéro
5
Pages
1215-1218
Langue
anglais
Résumé
Uveal melanoma is associated with a high mortality rate once metastases occur, with over >90% of metastatic patients dying within less than 1 year from metastases to the liver. The intraarterial hepatic (iah) administration of the alkylating agent fotemustine holds some promise with response rates of 36% and median survival of 15 months. Here, we investigated whether the DNA-repair-protein MGMT may be involved in the variability of response to fotemustine and temozolomide in uveal melanoma. Epigenetic inactivation of MGMT has been demonstrated to be a predictive marker for benefit from alkylating agent therapy in glioblastoma. We found a methylated MGMT promoter in 6% of liver metastases from 34 uveal melanoma patients. The mean MGMT activity measured in liver metastases with negligible liver tissue content was significantly lower than in liver tissue (146 versus 523 fmol/mg protein, p = 0.002). Expression of the MGMT protein was detectable in 50% of 88 metastases by immunohistochemistry on a tissue microarray. Expression was heterogeneous, and in accordance with MGMT activity data, usually lower than in the surrounding liver. Differential MGMT activity/expression between metastasis and liver tissue and more efficient depletion of MGMT with higher doses of alkylating agent therapy using iah delivery may provide the pharmacologic window for the higher response rate. However, these results do not support MGMT methylation status or protein expression as predictive markers for treatment outcome to iah chemotherapy with alkylating agents.
Mots-clé
Antineoplastic Agents,therapeutic use, DNA Methylation, DNA Modification Methylases,genetics, DNA Repair Enzymes,genetics, Humans, Immunohistochemistry, Liver Neoplasms,drug therapy,genetics,secondary, Melanoma,drug therapy,genetics,secondary, Predictive Value of Tests, Promoter Regions, Genetic, Protein Array Analysis, Tumor Markers, Biological,genetics, Tumor Suppressor Proteins,genetics, Uveal Neoplasms,pathology
Pubmed
Web of science
Création de la notice
11/02/2009 16:49
Dernière modification de la notice
20/03/2018 13:22
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