Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-9-12
pubmed:abstractText
KIT, platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs) are important clinical targets for tyrosine kinase inhibitors. The frequency of KIT and VEGFR2 amplification in glioblastomas is not known, and few data are available in any other human tumour type. We investigated 43 primary glioblastomas for KIT, VEGFR2, PDGFRA and EGFR amplification using fluorescence in situ hybridization. KIT was amplified in 47% and VEGFR2 in 39% of the glioblastomas, respectively, and PDGFRA in 29%. Thirty-five (81%) of the tumours had either KIT or EGFR amplification. KIT, PDGFRA and VEGFR2 amplifications were strongly associated (p < 0.0001 for each pairwise comparison), suggesting co-amplification, whereas no significant association was found with EGFR amplification. The four secondary glioblastomas arising from pre-existing lower grade astrocytic tumours investigated had KIT amplification but none had EGFR amplification. No mutations were detected with denaturing high-performance liquid chromatography in KIT exons 9, 11, 13 or 17, PDGFRA exons 12 and 18, or EGFR exons 18, 19 or 21. Glioblastomas with KIT, PDGFR or VEGFR2 amplification were associated with similar outcome to other glioblastomas. We conclude that KIT, PDGFRA and VEGFR2 are commonly amplified in primary glioblastoma and that they may also be amplified in secondary glioblastoma. Amplified kinases may be potential targets for tyrosine kinase inhibitor therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3417
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
207
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
224-31
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16021678-Adult, pubmed-meshheading:16021678-Aged, pubmed-meshheading:16021678-Brain Neoplasms, pubmed-meshheading:16021678-Endothelial Cells, pubmed-meshheading:16021678-Exons, pubmed-meshheading:16021678-Female, pubmed-meshheading:16021678-Gene Amplification, pubmed-meshheading:16021678-Genes, erbB-1, pubmed-meshheading:16021678-Glioblastoma, pubmed-meshheading:16021678-Humans, pubmed-meshheading:16021678-Immunohistochemistry, pubmed-meshheading:16021678-In Situ Hybridization, Fluorescence, pubmed-meshheading:16021678-Male, pubmed-meshheading:16021678-Middle Aged, pubmed-meshheading:16021678-Mutation, pubmed-meshheading:16021678-Phosphorylation, pubmed-meshheading:16021678-Protein-Tyrosine Kinases, pubmed-meshheading:16021678-Proto-Oncogene Proteins c-kit, pubmed-meshheading:16021678-Receptor, Platelet-Derived Growth Factor alpha, pubmed-meshheading:16021678-Survival Analysis, pubmed-meshheading:16021678-Vascular Endothelial Growth Factor Receptor-2
pubmed:year
2005
pubmed:articleTitle
Amplification of genes encoding KIT, PDGFRalpha and VEGFR2 receptor tyrosine kinases is frequent in glioblastoma multiforme.
pubmed:affiliation
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland. heikki.joensuu@hus.fi
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't