PURPOSE Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST. PATIENTS AND METH...

We recently identified the chimeric kinase FIP1L1-platelet-derived growth factor receptor alpha (PDGFRalpha) as a cause of the hypereosinophilic syndrome and of chronic eosinophilic leukemia. To investigate the role of FIP1L1-PDGFRA in the pathogenesis of acute leukemia, we screened 87 leukemia cell lines for the presence of FIP1L1-PDGFRA. One cell line, EOL-1, expressed the FIP1L1-PDGFRA fusio...

Activating mutations of KIT and platelet-derived growth factor receptor alpha (PDGFRA) are known to be alternative and mutually exclusive genetic events in the development of gastrointestinal stromal tumors (GISTs). We examined the effect of the mutations of these two genes on the gene expression profile of 22 GISTs using the oligonucleotide microarray. Mutations of KIT and PDGFRA were found in...

PDGFRA is mutated in 5%–10% of gastrointestinal stromal tumors (GISTs), the PDGFRA D842V mutation accounting for 60% of all PDGFRA mutations known in GISTs [1]. The DIMH842–845 and the IMH843–846 deletions represent 15% of all PDGFRA mutations. While the latter have been associated with sensitivity to imatinib, the PDGFRA D842V mutation confers primary resistance to imatinib [1–4], sunitinib [5...

BACKGROUND Primary eosinophlia associated with the FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukaemia (CEL) and affected patients are very sensitive to imatinib treatment. This study was undertaken in order to examine the prevalence and the associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 15 adult patients presenting ...

Activating mutations of platelet-derived growth factor receptor α (PDGFRA) are detected in a significant proportion of gastrointestinal stromal tumors (GISTs), in addition to the more frequent mutation in c-kit. GISTs with PDGFRA mutations have been found to have several characteristic morphological features, sometimes allowing to discriminate them from GISTs with c-kit mutations. Among these, ...

A novel oncogenic mutation (FIP1L1PDGFRA), which results in a constitutively activated platelet-derived growth factor receptor(PDGFRA), has been invariably associated with a primary eosinophilic disorder. The current study examines both the prevalence and the associated clinicopathologic features of this mutation in a cohort of 89 adult patients presenting with an absolute eosinophil count (AEC...

BACKGROUND There is an ongoing search for new therapeutic targets in invasive non-resectable thymic tumours because of the low response rates in current chemotherapeutic treatment modalities. In this study, the possibility that platelet-derived growth factor receptor A (PDGFRA) and/ or PDGFRB may represent potential therapeutic targets in epithelial tumours of the thymus was investigated. PAT...

Imatinib mesylate is effective in the treatment of hematologic malignancies that are characterized by either abl- or PDGFR beta- activating mutations. The drug is also active in a subset of patients with eosinophilic disorders and systemic mast cell disease (SMCD). Recently, a novel tyrosine kinase that is generated from fusion of the Fip1-like 1 (FIP1L1) and PDGFR alpha (PDGFRA) genes has been...

AIM To study the immunoexpression and mutational status of c-KIT and PDGFRA in a series of benign and malignant phyllodes tumours of the breast. MATERIAL/METHODS Nineteen phyllodes tumours (13 benign and six malignant) were analysed by immunohistochemistry for the expression of c-KIT and PDGFRA. Direct sequencing of exons 9, 11, 13, and 17 of the c-KIT gene and exons 12 and 18 of PDGFRA was p...