Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-3-8
pubmed:abstractText
Glioblastoma, the most aggressive primary brain tumor in humans, exhibits a large degree of molecular heterogeneity. Understanding the molecular pathology of a tumor and its linkage to behavior is an important foundation for developing and evaluating approaches to clinical management. Here we integrate array-comparative genomic hybridization and array-based gene expression profiles to identify relationships between DNA copy number aberrations, gene expression alterations, and survival in 34 patients with glioblastoma. Unsupervised clustering on either profile resulted in similar groups of patients, and groups defined by either method were associated with survival. The high concordance between these separate molecular classifications suggested a strong association between alterations on the DNA and RNA levels. We therefore investigated relationships between DNA copy number and gene expression changes. Loss of chromosome 10, a predominant genetic change, was associated not only with changes in the expression of genes located on chromosome 10 but also with genome-wide differences in gene expression. We found that CHI3L1/YKL-40 was significantly associated with both chromosome 10 copy number loss and poorer survival. Immortalized human astrocytes stably transfected with CHI3L1/YKL-40 exhibited changes in gene expression similar to patterns observed in human tumors and conferred radioresistance and increased invasion in vitro. Taken together, the results indicate that integrating DNA and mRNA-based tumor profiles offers the potential for a clinically relevant classification more robust than either method alone and provides a basis for identifying genes important in glioma pathogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1678-86
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15753362-Adipokines, pubmed-meshheading:15753362-Astrocytes, pubmed-meshheading:15753362-Brain Neoplasms, pubmed-meshheading:15753362-Cells, Cultured, pubmed-meshheading:15753362-Chromosomes, Human, Pair 10, pubmed-meshheading:15753362-DNA, pubmed-meshheading:15753362-Gene Expression Profiling, pubmed-meshheading:15753362-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15753362-Glioblastoma, pubmed-meshheading:15753362-Glycoproteins, pubmed-meshheading:15753362-Humans, pubmed-meshheading:15753362-Lectins, pubmed-meshheading:15753362-Neoplasm Invasiveness, pubmed-meshheading:15753362-Nucleic Acid Hybridization, pubmed-meshheading:15753362-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15753362-RNA, pubmed-meshheading:15753362-Radiation Tolerance, pubmed-meshheading:15753362-Survival Rate
pubmed:year
2005
pubmed:articleTitle
Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of glioblastoma.
pubmed:affiliation
Department of Neurological Surgery (Brain Tumor Research Center), University of California, School of Medicine, San Francisco, California, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.