CONCORDANT METHYLATION OF THE ER AND N33 GENES IN GLIOBLASTOMA-MULTIFORME

Methylation of promoter-associated CpG islands appears to be a potenti al way by which tumor suppressor genes are inactivated in cancer. Usin g Southern blot analysis, we have studied the methylation of several g enes in glioblastoma multiforme (GBM), trying to determine their contr ibution to tumorigenesis. Genes studied included the estrogen receptor (ER), N33, the candidate tumor-suppressors P15, P16 and HIC1 and a co ntrol gene, c-abl, Hypermethylation of N33, ER, HIC1, P16, P15 and c-a bl were found in 61%, 59%, 60%, 5%, 2% and 0% of GEM respectively. HIC 1 methylation was detected in normal brain as well, but appeared to be more extensive in tumors. ER and N33 methylation were significantly m ore frequent in tumors from individuals over the age of 40 (70% and 88 % vs 36% and 14%). In addition, there was a strong association between EX and N33 methylation, which were concordant in 81% of the cases (P< 0.01). ER and N33 methylation in GEM may therefore appear as a result of shared etiologic factors, which may relate in part to aging cell p opulations in the brain.