EZH2-regulated DAB2IP is a medulloblastoma tumor suppressor and a positive marker for survival

Michiel Smits, Sjoerd van Rijn, Esther Hulleman, Dennis Biesmans, Dannis van Vuurden, Marcel Kool, Christine Haberler, Eleanora Aronica, William P. Vandertop, David P. Noske, Thomas Wurdinger

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements, the molecular mechanisms driving medulloblastoma are not fully understood and further elucidation could provide cues to improve outcome prediction and therapeutic approaches.

Experimental design: Here, we conducted a meta-analysis of mouse and human medulloblastoma gene expression data sets, to identify potential medulloblastoma tumor suppressor genes.

Results: We identified DAB2IP, a member of the RAS-GTPase-activating protein family (RAS GAP), and showed that DAB2IP expression is repressed in medulloblastoma by EZH2-induced trimethylation. Moreover, we observed that reduced DAB2IP expression correlates significantly with a poor overall survival of patients with medulloblastoma, independent of metastatic stage. Finally, we showed that ectopic DAB2IP expression enhances stress-induced apoptosis in medulloblastoma cells and that reduced expression of DAB2IP in medulloblastoma cells conveys resistance to irradiation-induced cell death.

Conclusion: These results suggest that repression of DAB2IP may at least partly protect medulloblastoma cells from apoptotic cell death. Moreover, DAB2IP may represent a molecular marker to distinguish patients with medulloblastoma at high risk from those with a longer survival prognosis.
Original languageEnglish
Pages (from-to)4048-4058
JournalClin Cancer Res
Volume18
Issue number15
DOIs
Publication statusPublished - 1 Aug 2012

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