DNA methylation of multiple genes in vestibular schwannoma:: Relationship with clinical and radiological findings

Hypothesis: The purpose of this study was to examine the DNA methylation profile of several genes in a series of vestibular schwannomas, and to analyze its relationship with clinical and radiological features. Background: Aberrant methylation of promoter regions is a major mechanism for silencing of tumor suppressor genes in several tumors. There is limited information about methylation status in vestibular schwannoma, with no clinical or radiological implications described to date. Methods: The methylation status of 16 tumor-related genes including RASSF1A, RAR-B, VHL, PTEN, HMLH1, RB1, TP16, CASP8, ER, TIMP3, MGMT, DAPK, TP73, GSTP1, TP14, and THBS1 was examined in a series of 22 vestibular schwannomas. The bisulfite modification of genomic DNA was performed. Clinical and radiological features were compared with the methylation results. Results: Methylation values from 9% to 27% were found in 12 of 16 genes tested, including RASSF1A, VHL, PTEN, TP16, CASP8, TIMP3, MGMT, DAPK, THBS1, HMLH1, TP73, and GSTP1. A significant association was found between CASP8 and RASSF1A methylation. Methylation of CASP8 was associated with the patient's age and the tumor size. Methylation of TP73 was associated with hearing loss. RASSF1A methylation was inversely correlated with the clinical growth index. Conclusion: Aberrant methylation of tumor-related genes may play a role in the development of vestibular schwannomas. Our results may provide useful clues to the development of prognostic assays for these tumors.