gms | German Medical Science

Question: Glioblastoma is the most common malignant primary brain tumor with a dismal prognosis of 14.6 months. A small percentage of patients shows an increased survival time of >3 years. One possible explanation is the methylation pattern of the regulatory elements of the MGMT gene, which has been linked to a better prognosis. In this study we evaluate the methylation pattern of all CpG islands of the promoter and enhancer regions of the MGMT Gene using bisulfite-sequencing, and compare results in patients who survived <1 year (short term survivors) with patients who survived >3 years (long term survivors).

Methods: The methylation pattern of glioblastoma tissue from 15 long term survivors was analyzed using bisulfite treatment and Sanger sequencing and compared to 19 short term survivors. Statistical analysis was performed with the rank sum test. To correct for multiple comparisons, false discovery rate (fdr) was used.

Results: Twelve long term survivors showed at least partial MGMT methylation. The rank sum test revealed significant differences for CpGs 75, 76, 77 and 80 (0.01<p<0.02, fdr corrected) between long term and short term survivors.

Conclusions: Our results regarding the association of prognosis and methylation pattern are similar to those previously published. However, our results indicate that other CpG islands may be more closely linked to prognosis than those previously reported (76, 78, 82, 83, 87). The number of cases in this ongoing study is currently being increased to enhance the statistical power.