Analysis of cytogenetic aberrations in sporadic vestibular schwannoma by comparative genomic hybridization.
Vestibular schwannomas (VS) are benign tumors of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). The NF2 gene is a tumor suppressor gene located on chromosome 22. Loss of the NF2 protein product, Merlin, is universal in both sporadic and NF2-related schwannomas and the loss or mutation of the gene is the only established causative event underlying schwannoma formation. Comparative genomic hybridization (CGH) was used to screen 20 sporadic VS to identify additional chromosomal regions that may harbor genes involved in VS-tumorigenesis. The most common change were losses on chromosome 22q. Additionally, losses were observed on chromosome 9p indicating a possible participation of the CDKN2A tumor suppressor gene in the genesis of VS. Gains were observed on 17q, 19p and 19q, which have been reported before in malignant peripheral nerve sheath tumors that are associated with neurofibromatosis type 1. Importantly, high level amplifications have been observed on 16p and 16q as well as on 9q, suggesting the possible involvement of several oncogenes in the tumorigenesis of VS. Our data suggest the involvement of various oncogenes and tumor suppressor genes might play a role in the genesis of the vestibular schwannomas apart from the inactivation of the NF2 gene.
Koutsimpelas
Dimitrios
D
Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55101 Mainz, Germany. koutsimpelas@hno.klinik.uni-mainz.de
Felmeden
Uwe
U
Mann
Wolf J
WJ
Brieger
Jürgen
J
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D003582:Cytogenetics / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009464:Neuroma, Acoustic / Q000175:diagnosis* / Q000235:genetics*; D012189:Retrospective Studies