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 Neuro-Oncology
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:
https://lup.lub.lu.se/record/540707
- author
- 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
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- therapeutic target, chromosome, glioma, microarray
- in
- Journal of Neuro-Oncology
- volume
- 85
- issue
- J1
- pages
- 11 - 24
- publisher
- Springer
- external identifiers
-
- wos:000249458000002
- scopus:34548809815
- pmid:17634744
- ISSN
- 1573-7373
- DOI
- 10.1007/s11060-007-9383-6
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division V (013230900), Division IV (013230800), Genetics (Closed 2011) (011005100), Computational biology and biological physics (000006113), Division of Clinical Genetics (013022003), Oncology, MV (013035000), Faculty of Medicine (000022000), Pathology, (Lund) (013030000), Neurosurgery (013026000)
- 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
- 2016-04-01 16:40:04
- date last changed
- 2024-03-15 09:50:30
@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}},
keywords = {{therapeutic target; chromosome; glioma; microarray}},
language = {{eng}},
number = {{J1}},
pages = {{11--24}},
publisher = {{Springer}},
series = {{Journal of Neuro-Oncology}},
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}},
doi = {{10.1007/s11060-007-9383-6}},
volume = {{85}},
year = {{2007}},
}