CpG island methylation in sporadic and neurofibromatis type 2-associated schwannomas

Purpose: The purpose of this research was to examine the DNA methylation profile of schwannomas. Experimental Design: We examined the DNA methylation status of 12 tumor-related genes (NF2, RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1, caspase-8, TP53, and GSTP1) in 44 sporadic and/or NF2-associated schwannomas using methylation-specific PCR. Results: The most frequently methylated genes were THBS1 (36 %), p 73 (27 %), MGMT (20 %), NF2 and TIMP-3 (18%). The RB1/p16INK4a gene pair displayed aberrant methylayed alleles in 15% of cases, whereas methylation was relatively rare in the other genes (<5%). Methylation was tumor specific because it was absent in two nonneoplastic nerve sheath samples and two normeoplastic brain samples studied as controls. Conclusions: Our findings indicate that aberrant methylation seems to be a mechanism for NF2 gene inactivation, considered an early step in schwarmoma tumorigenesis, and as well, aberrant hypermethylation of other tumor-related genes might represent secondary events that also contribute to the development of these tumors.