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Microarray analysis of gliomas reveals chromosomal position-associated gene expression patterns and identifies potential immunotherapy targets.

Author:
  • Oscar Persson
  • Morten Krogh
  • Lao Saal
  • Elisabet Englund
  • Jian Liu
  • Ramon Parsons
  • Nils Mandahl
  • Åke Borg
  • Bengt Widegren
  • Leif Salford
Publishing year: 2007
Language: English
Pages: 11-24
Publication/Series: Journal of Neurooncology
Volume: 85
Issue: J1
Document type: Journal article
Publisher: Springer

Abstract english

Gliomas are among the most aggressive malignant tumors and the most refractory to therapy, in part due to the propensity for malignant cells to disseminate diffusely throughout the brain. Here, we have used 27 K cDNA microarrays to investigate global gene expression changes between normal brain and high-grade glioma (glioblastoma multiforme) to try and better understand gliomagenesis and to identify new therapeutic targets. We have also included smaller groups of grade II and grade III tumors of mixed astrocytic and oligodendroglial origin as comparison. We found that the expression of hundreds of genes was significantly correlated to each group, and employed a naive Bayesian classifier with leave-one-out cross-validation to accurately classify the samples. We developed a novel algorithm to analyze the gene expression data from the perspective of chromosomal position, and identified distinct regions of the genome that displayed coordinated expression patterns that correlated significantly to tumor grade. The regions identified corresponded to previously known genetic copy number changes in glioma (e.g. 10q23, 10q25, 7q, 7p) as well as regions not previously associated significantly with glioma (e.g. 1p13, 6p22). Furthermore, to enrich for more suitable targets for therapy, we took a bioinformatics approach and annotated our signatures with two published datasets that identified membrane/secreted genes from cytosolic genes. The resulting focused list of 31 genes included interesting novel potential targets as well as several proteins already being investigated for immunotherapy (e.g. CD44 and tenascin-C). Software for the chromosome analysis was developed and is freely available at http://base.thep.lu.se.

Keywords

  • Clinical Medicine
  • Medical Genetics
  • Other Clinical Medicine
  • therapeutic target
  • chromosome
  • glioma
  • microarray

Other

Published
  • CREATE Health
  • ISSN: 1573-7373
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90