CpG island methylation in sporadic and neurofibromatis type 2-associated schwannomas.
OBJECTIVE
The purpose of this research was to examine the DNA methylation profile of schwannomas.


METHODS
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.
Gonzalez-Gomez
Pilar
P
Department of C. Experimental, Laboratorio Oncogenetica Molecular, Hospital Universitario La Paz, Madrid, Spain.
Bello
M Josefa
MJ
Alonso
M Eva
ME
Lomas
Jesus
J
Arjona
Dolores
D
Campos
Jose M de
JM
Vaquero
Jesus
J
Isla
Alberto
A
Lassaletta
Luis
L
Gutierrez
Manuel
M
Sarasa
Jose L
JL
Rey
Juan A
JA
D000328:Adult; D000368:Aged; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000235:genetics*; D016518:Neurofibromatosis 2 / Q000235:genetics*; D016133:Polymerase Chain Reaction
D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide