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


CONCLUSIONS
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.
Lassaletta
Luis
L
Department of Otolaryngology, Laboratorio Oncogenetica Molecular, La Paz University Hospital, Madrid, Spain. luikilassa@yahoo.com
Bello
M Josefa
MJ
Del Río
Laura
L
Alfonso
Carolina
C
Roda
Jose Maria
JM
Rey
Juan A
JA
Gavilan
Javier
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001309:Auditory Threshold / Q000502:physiology; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009464:Neuroma, Acoustic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011859:Radiography