This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gonzalez-Gomez, P. Articles by Rey, J. A. Search for Related Content PubMed PubMed Citation Articles by Gonzalez-Gomez, P. Articles by Rey, J. A.

CpG Island Methylation in Sporadic and Neurofibromatis Type 2-Associated Schwannomas

¹ Department of C. Experimental, Laboratorio Oncogenetica Molecular,
² Department of Neurosurgery,
³ Department of Otolaryngology, and
⁴ Department of Pathology, Hospital Universitario La Paz, Madrid;
⁵ Department of Neurosurgey, Hospital del Rio Hortega, Valladolid;
⁶ Department of Neurosurgery, Clinica Puerta de Hierro, Madrid; and
⁷ Department of Pathology, Fundacion Jimenez Diaz, Madrid, Spain

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%), p73 (27%), MGMT (20%), NF2 (18%), 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 nonneoplastic 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 schwannoma tumorigenesis, and as well, aberrant hypermethylation of other tumor-related genes might represent secondary events that also contribute to the development of these tumors.