| In addition to accumulating evidences of genetic lesions in carcinogenesis, epigenetic changes also play an important role in cancer development. This study investigated the potential involvement of hypermethylation of promoter CpG islands, one of epigenetic changes, in the carcinogenesis of non-astrocytic gliomas.; In the first part of study, eleven tumor-related genes were examined by methylation-specific PCR in oligodendroglial tumors and the findings were correlated with loss of 1p/19q status. The results showed hypermethylation is a common event in the pathogenesis of oligodendroglial tumors. Hypermethylation of O6-methylguanine methyltransferase (MGMT) occurred in 60% tumors and correlated with loss of 1p/19q status, suggesting it may contribute to the tumorigenesis of oligodendroglial tumors and be responsible for the chemosensitivity of those tumors. The results also showed hypermethylation of p16INK4a, p15INK4b and concurrent hypermethylation of at least two genes mainly occurs in anaplastic oligodendroglial tumors and is associated with tumor grade.; In the second part of study, detailed genetic analysis was performed on the TP73 gene in oligodendroglial tumors. The RNA expression showed inactivation of TP73 gene occurred at transcript level, ten of 24 (42%) tumors showed negligible to more than 5-fold reduction in TP73 expression. No mutation was found whereas 39% of tumors were hypermethylated, and six of ten (60%) tumors with negligible or decreased levels of TP73 transcripts were methylation-positive. It is suggested that TP73 inactivation is associated with promoter hypermethylation and loss or reduced TP73 transcript expression may contribute to the tumorigenesis of oligodendroglial tumors.; In third part of study, I performed detailed methylation study in ependymal tumors, another type of non-astrocytic gliomas and compared the results with those found in oligodendroglial tumors. Thirteen tumor-related genes were examined, and 50% of tumors showed methylation in at least one gene. hMLH1 gene was methylated in a 23% of tumors whereas it was not methylated in oligodendroglial tumors. (Abstract shortened by UMI.)... |
