High-resolution genome-wide mapping of genetic alterations in human glial brain tumors

Markus Bredel, Claudia Bredel, Dejan Juric, Griffith R. Harsh, Hannes Vogel, Lawrence D. Recht, Branimir I. Sikic

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4088-4096
Number of pages9
JournalCancer Research
Volume65
Issue number10
DOIs
StatePublished - May 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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