P04.23PROMOTOR HYPERMETHYLATION OF MGMT, P15, P16 AND RB1 IN PILOCYTIC ASTROCYTOMA

OBJECTIVE: Pilocytic astrocytomas are WHO grade I gliomas occurring mainly in the childhood and adolescent ages. Promoter hypermethylation of tumor suppressor genes is a very common mechanism in CNS neoplasias which is generally associated with their transcriptional silencing. MATERIAL & METHODS: Using MS-PCR, we analyzed the methylation status of the tumor suppressor genes p15, p16, RB1, and MGMT in n = 18 pilocytic astrocytomas. Furthermore, all tumour samples were tested for the R132H mutation of the IDH1 gene by use of immunohistochemical staining. The results of the MGMT methylation analysis were correlated with the individual clinical and demographical data as well as with the progression-free (PFS) and overall survival (OS). RESULTS: Each of the 18 pilocytic astrocytoma specimen presented unmethylated in the investigated promoter regions of p16 and RB1. For the p15 gene, 1/18 tumor sample showed a positive methylation signal (5.6%). This single case presented with an extraordinary aggressive clinical course including frequent local recurrences with meningeal metastases but without tumor upgrading. For the MGMT gene, however, methylation frequency was 44.5% (8/18). Interestingly, when stratified for the MGMT methylation status, the group of methylated pilocytic astrocytomas showed a significantly shortened PFS in the Kaplan-Meier curve compared to their unmethylated counterparts (11.75 Months vs. 74.0 Months; p = 0.041; univariate log rank test). CONCLUSION: Epigenetic mechanisms, in particular the promoter methylation of the MGMT and p15 genes, contrary to the perception of literatur that pilocytic astrocytomas are commonly unmethylated, may obviously have an impact on the clinical course in pilocytic astrocytoma disease.