Previous studies have shown that activating mutations of c-KIT/PDGFRA, potential therapeutic targets for imatinib mesylate, are implicated in the pathophysiology of gastrointestinal stromal tumours (GISTs). In this study, GISTs from 37 patients enrolled in an European Organisation for Research and Treatment of Cancer (EORTC) phase I/II clinical study of imatinib were examined for mutations of c...

Introduction. Gastrointestinal stromal tumors (GISTs) are characterized at the molecular level by c-kit or PDGFRA oncogene mutations. Although GISTs raised major interest in past decades, population-based studies are still rare. Materials and Methods. All GISTs diagnosed in Southern Switzerland (1999-2005) were identified using Ticino Cancer Registry and analysed for c-kit and PDGFRA mutations....

The localized developmental expression of murine platelet-derived growth factor A (PDGF-A) was compared to that of its receptor (Pdgfra). Our in situ hybridization study included germ layers of primitive streak embryos, early axial structures (dermatome, myotome, sclerotome, floor plate), the skin and some of its derivatives (hair and mammary gland), the developing forelimb, the branchial arche...

The outcome for children with high-grade gliomas (HGG) remains dismal, with a 2-year survival rate of only 10% to 30%. Diffuse intrinsic pontine glioma (DIPG) comprise a subset of HGG that arise in the brainstem almost exclusively in children. Genome-wide analyses of copy number imbalances previously showed that platelet-derived growth factor receptor α (PDGFRA) is the most frequent target of f...

Sorafenib has substantial clinical activity as third- or fourth-line treatment of imatinib- and sunitinib-resistant gastrointestinal stromal tumors (GIST). Because sorafenib targets both angiogenesis-related kinases (VEGFR) and the pathogenetic kinases found in GIST (KIT or PDGFRA), the molecular basis for sorafenib efficacy in this setting remains unknown. We sought to determine the spectrum o...

We are studying the chromosomal structure of three developmental mutations, dominant spotting (W), patch (Ph), and rump white (Rw) on mouse chromosome 5. These mutations are clustered in a region containing three genes encoding tyrosine kinase receptors (Kit, Pdgfra, and Flk1). Using probes for these genes and for a closely linked locus, D5Mn125, we established a high-resolution physical map co...

We recently characterized gene expression patterns in gastrointestinal stromal tumors (GISTs) using cDNA microarrays, and found that the gene FLJ10261 (DOG1, discovered on GIST-1), encoding a hypothetical protein, was specifically expressed in GISTs. The immunoreactivity of a rabbit antiserum to synthetic DOG1 peptides was assessed on two soft tissue tumor microarrays. The tissue microarrays in...

AIMS The embryonic epicardium is a source of smooth muscle cells and fibroblasts of the coronary vasculature and of the myocardium, but the signalling pathways that control mobilization and differentiation of epicardial cells are only partly known. We aimed to (re-)evaluate the relevance of canonical Wnt-, Hedgehog (Hh)-, Fibroblast growth factor receptor (Fgfr)1/2-, and platelet-derived growth...

The platelet-derived growth factor alpha-receptor (PDGFR-alpha) displays a lineage-specific expression pattern in the mouse embryo and is required for normal development of mesoderm and cephalic neural crest derivatives. The purpose of the present study was to demonstrate the in vivo promoter function of genomic DNA fragments representing the 5'-flanking part of the human PDGFRA gene. 2.2, 0.9 ...

Goal. Surgeons that remove a typical polyp from the stomach or small intestine should be reluctant to accept a diagnosis of GIST just because there is a mutation in platelet-derived growth factor receptor alfa (PDGFRA). Background. A subtype of gastric and intestinal polyps is denoted as inflammatory fibroid polyp (IFP). In some of these cases a mutation in PDGFRA is found, leading to the diagn...