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

Verena Voelter*, Annie Claire Diserens, Alexandre Moulin, Georg Nagel, Pu Yan, Eugenia Migliavacca, Donata Rimoldi, Marie France Hamou, Bernd Kaina, Serge Leyvraz, Monika E. Hegi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1215-1218
Number of pages4
JournalInternational Journal of Cancer
Issue number5
StatePublished - Sep 1 2008
Externally publishedYes


  • Fotemustine
  • Liver metastases
  • MGMT gene silencing
  • Uveal melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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