PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas Journal Article
| Authors: | Ozawa, T.; Brennan, C. W.; Wang, L.; Squatrito, M.; Sasayama, T.; Nakada, M.; Huse, J. T.; Pedraza, A.; Utsuki, S.; Yasui, Y.; Tandon, A.; Fomchenko, E. I.; Oka, H.; Levine, R. L.; Fujii, K.; Ladanyi, M.; Holland, E. C. |
| Article Title: | PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas |
| Abstract: | Gene rearrangement in the form of an intragenic deletion is the primary mechanism of oncogenic mutation of the epidermal growth factor receptor (EGFR) gene in gliomas. However, the incidence of platelet-derived growth factor receptor-α (PDGFRA) gene rearrangement in these tumors is unknown. We investigated the PDGFRA locus in PDGFRA-amplified gliomas and identified two rearrangements, including the first case of a gene fusion between kinase insert domain receptor (KDR) (VEGFRII) and the PDGFRA gene, and six cases of PDGFRAΔ8, 9, an intragenic deletion rearrangement. The PDGFRAΔ8, 9 mutant was common, being present in 40% of the glioblastoma multiformes (GBMs) with PDGFRA amplification. Tumors with these two types of PDGFRA rearrangement displayed histologic features of oligodendroglioma, and the gene products of both rearrangements showed constitutively elevated tyrosine kinase activity and transforming potential that was reversed by PDGFR blockade. These results suggest the possibility that these PDGFRA mutants behave as oncogenes in this subset of gliomas, and that the prevalence of such rearrangements may have been considerably underestimated. © 2010 by Cold Spring Harbor Laboratory Press. |
| Keywords: | signal transduction; mitogen activated protein kinase; human tissue; gene mutation; gene deletion; genetics; mutation; pyridines; molecular genetics; glioma; protein domain; metabolism; imatinib; platelet derived growth factor alpha receptor; receptor, platelet-derived growth factor alpha; gene amplification; protein kinase inhibitor; gene locus; gene product; drug effect; pathology; enzyme activity; protein tyrosine kinase; pyrimidines; vasculotropin receptor 2; phosphorylation; phosphatidylinositol 3 kinase; protein kinase inhibitors; oncogene; gene rearrangement; amino acid sequence; molecular sequence data; glioblastoma; nucleotide sequence; 1-phosphatidylinositol 3-kinase; receptor tyrosine kinase; gene fusion; vatalanib; base sequence; oligodendroglioma; protein-tyrosine kinases; piperazines; gene dosage; piperazine derivative; pyrimidine derivative; mitogen-activated protein kinases; pyridine derivative; genetic identification; phthalazine derivative; phthalazines; genetic transformation; copy number alteration; pdgfra gene rearrangement; transformation, genetic |
| Journal Title: | Genes and Development |
| Volume: | 24 |
| Issue: | 19 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2010-10-01 |
| Start Page: | 2205 |
| End Page: | 2218 |
| Language: | English |
| DOI: | 10.1101/gad.1972310 |
| PUBMED: | 20889717 |
| PROVIDER: | scopus |
| PMCID: | PMC2947772 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: GEDEE" - "Source: Scopus" |
