title: Molecular classification of human gliomas using matrix-based comparative genomic hybridization.
abstract: Gliomas are the most frequent primary brain tumors and comprise a group of morphologically, biologically and clinically heterogeneous neoplasms. The different glioma types are associated with distinct genetic aberrations, which may provide useful information for tumor classification as well as prediction of prognosis and response to therapy. To facilitate the molecular classification of gliomas, we established a genomic microarray that consists of bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) clones representing tumor suppressor genes, proto-oncogenes and chromosomal regions frequently gained or lost in gliomas. In addition, reference clones distributed evenly throughout the genome in approximately 15 Mbp intervals were spotted on the microarray. These customized microarrays were used for matrix-based comparative genomic hybridization (matrix CGH) analysis of 70 gliomas. Matrix CGH findings were validated by molecular genetic analyses of candidate genes, loss of heterozygosity studies and chromosomal CGH. Our results indicate that matrix CGH allows for the sensitive and specific detection of gene amplifications as well as low-level copy number gains and losses in clinical glioma samples. Furthermore, molecular classification based on matrix CGH data closely paralleled histological classification and was able to distinguish with few exceptions between diffuse astrocytomas and oligodendrogliomas, anaplastic astrocytomas and anaplastic oligodendrogliomas, anaplastic oligodendrogliomas and glioblastomas, as well as primary and secondary glioblastomas. Thus, matrix CGH is a powerful technique that allows for an automated genomic profiling of gliomas and represents a promising new tool for their molecular classification.
authors.affiliation: Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Roerig
authors.forename: Michelle
authors.initials: M
authors.lastname: Nessling
authors.forename: Bernhard
authors.initials: B
authors.lastname: Radlwimmer
authors.forename: Stefan
authors.initials: S
authors.lastname: Joos
authors.forename: Gunnar
authors.initials: G
authors.lastname: Wrobel
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwaenen
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000145:classification* / Q000235:genetics; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D002877:Chromosomes, Human; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005784:Gene Amplification; D015894:Genome, Human; D015698:Genomic Library; D005910:Glioma / Q000145:classification* / Q000235:genetics; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm