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

Persson, Oscar LU ; Krogh, Morten LU ; Saal, Lao LU ; Englund, Elisabet LU ; Liu, Jian LU ; Parsons, Ramon; Mandahl, Nils LU ; Borg, Åke LU ; Widegren, Bengt LU and Salford, Leif LU (2007) In Journal of Neurooncology 85(J1). p.11-24
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
therapeutic target, chromosome, glioma, microarray
in
Journal of Neurooncology
volume
85
issue
J1
pages
11 - 24
publisher
Springer
external identifiers
  • wos:000249458000002
  • scopus:34548809815
ISSN
1573-7373
DOI
10.1007/s11060-007-9383-6
project
CREATE Health
language
English
LU publication?
yes
id
31219378-009a-484e-b931-1762e5c33ece (old id 540707)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17634744&dopt=Abstract
date added to LUP
2007-12-19 13:23:07
date last changed
2017-09-24 04:29:16
@article{31219378-009a-484e-b931-1762e5c33ece,
  abstract     = {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.},
  author       = {Persson, Oscar and Krogh, Morten and Saal, Lao and Englund, Elisabet and Liu, Jian and Parsons, Ramon and Mandahl, Nils and Borg, Åke and Widegren, Bengt and Salford, Leif},
  issn         = {1573-7373},
  keyword      = {therapeutic target,chromosome,glioma,microarray},
  language     = {eng},
  number       = {J1},
  pages        = {11--24},
  publisher    = {Springer},
  series       = {Journal of Neurooncology},
  title        = {Microarray analysis of gliomas reveals chromosomal position-associated gene expression patterns and identifies potential immunotherapy targets.},
  url          = {http://dx.doi.org/10.1007/s11060-007-9383-6},
  volume       = {85},
  year         = {2007},
}