Comprehensive characterization of genomic aberrations in gangliogliomas by CGH, array-based CGH and interphase FISH.
Gangliogliomas are generally benign neuroepithelial tumors composed of dysplastic neuronal and neoplastic glial elements. We screened 61 gangliogliomas [World Health Organization (WHO) grade I] for genomic alterations by chromosomal and array-based comparative genomic hybridization (CGH). Aberrations were detected in 66% of gangliogliomas (mean +/- SEM = 2.5 +/- 0.5 alterations/tumor). Frequent gains were on chromosomes 7 (21%), 5 (16%), 8 (13%), 12 (12%); frequent losses on 22q (16%), 9 (10%), 10 (8%). Recurrent partial imbalances comprised the minimal overlapping regions dim(10)(q25) and enh(12)(q13.3-q14.1). Unsupervised cluster analysis of genomic profiles detected two major subgroups (group I: complete gain of 7 and additional gains of 5, 8 or 12; group II: no major recurring imbalances, mainly losses). A comparison with low-grade gliomas (astrocytomas WHO grade II) showed chromosome 5 gain to be significantly more frequent in gangliogliomas. Interphase fluorescence in situ hybridization (FISH) identified the aberrations to be contained in a subpopulation of glial but not in neuronal cells. Two gangliogliomas and their anaplastic recurrences (WHO grade III) were analyzed. Losses of CDKN2A/B and DMBT1 or a gain/amplification of CDK4 found in the anaplastic tumors were already present in the respective gangliogliomas by array CGH and interphase FISH. In summary, genomic profiling in a large series of gangliogliomas could distinguish genetic subgroups even in this low-grade tumor.
Hoischen
Alexander
A
Department of Human Genetics, Rheinische Friedrich-Wilhelms-University of Zürich, Zürich, Switerland.
Ehrler
Marion
M
Fassunke
Jana
J
Simon
Matthias
M
Baudis
Michael
M
Landwehr
Christina
C
Radlwimmer
Bernhard
B
Lichter
Peter
P
Schramm
Johannes
J
Becker
Albert J
AJ
Weber
Ruthild G
RG
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D018303:Ganglioglioma / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization