Recurrent cytogenetic aberrations in central neurocytomas and their biological relevance.
Central neurocytomas are rare central nervous system neoplasms. Since the first description, approximately 500 cases of these tumors have been published to date. Nevertheless, only a limited number of genetic studies on these tumors have been reported. Here we investigated 20 "typical" central neurocytomas using array-based comparative genomic hybridization (array-CGH) with the GenoSensor Array 300. The functional significance of detected chromosomal aberrations harboring potent candidate genes was also examined at the mRNA expression level. Each tumor examined displayed DNA copy-number aberrations (CNAs), and mean number of CNAs per tumor was 38.1 +/- 7.1 (range 19-53). Frequent gains were mapped at 2p24.1-22.1, 10q23.3-26.3, 11q23-25, and 18q21.3-qter. Frequent losses were identified at 1pter-36.3, 1p34.3, 6q13-21, 12q23-qter, 17p13.3, 17q11-23, and 20pter-12.3. There were 10 gained and 23 lost single DNA clones affecting >or=40% of samples tested. mRNA expression levels of 24 selected candidate genes harbored in these imbalanced clones were analyzed. MYCN, PTEN, and OR5BF1 were strongly overexpressed, whereas BIN1, SNRPN, and HRAS were found to be strongly underrepresented at the transcriptional level. Thus these data support that MYCN oncogene gain/overexpression accompanied by reduced expression of BIN1 tumor suppressor may contribute to central neurocytoma tumorigenesis.
Korshunov
Andrey
A
Department of Neuropathology, NN Burdenko Neurosurgical Institute, Fadeeva Str. 5, Moscow, 125047, Russia. akorshunov@nsi.ru
Sycheva
Regina
R
Golanov
Andrey
A
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology*; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018306:Neurocytoma / Q000235:genetics* / Q000473:pathology*; D009693:Nucleic Acid Hybridization / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human