title: High-resolution genome-wide mapping of genetic alterations in human glial brain tumors.
abstract: High-resolution genome-wide mapping of exact boundaries of chromosomal alterations should facilitate the localization and identification of genes involved in gliomagenesis and may characterize genetic subgroups of glial brain tumors. We have done such mapping using cDNA microarray-based comparative genomic hybridization technology to profile copy number alterations across 42,000 mapped human cDNA clones, in a series of 54 gliomas of varying histogenesis and tumor grade. This gene-by-gene approach permitted the precise sizing of critical amplicons and deletions and the detection of multiple new genetic aberrations. It has also revealed recurrent patterns of occurrence of distinct chromosomal aberrations as well as their interrelationships and showed that gliomas can be clustered into distinct genetic subgroups. A subset of detected alterations was shown predominantly associated with either astrocytic or oligodendrocytic tumor phenotype. Finally, five novel minimally deleted regions were identified in a subset of tumors, containing putative candidate tumor suppressor genes (TOPORS, FANCG, RAD51, TP53BP1, and BIK) that could have a role in gliomagenesis.
authors.affiliation: Division of Oncology, Center for Clinical Sciences Research, Stanford University School of Medicine, Stanford, California 94305-5151, USA. mbredel@stanford.edu
authors.forename: Markus
authors.initials: M
authors.lastname: Bredel
authors.forename: Claudia
authors.initials: C
authors.lastname: Bredel
authors.forename: Dejan
authors.initials: D
authors.lastname: Juric
authors.forename: Griffith R
authors.initials: GR
authors.lastname: Harsh
authors.forename: Hannes
authors.initials: H
authors.lastname: Vogel
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Recht
authors.forename: Branimir I
authors.initials: BI
authors.lastname: Sikic
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015894:Genome, Human; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis