Abstract Pediatric high-grade glioma (pHGG) is an incurable disease with a median survival of less than 6 months post-progression and no effective targeted therapy. PDGFRA commonly altered in pHGG, but targeting this has been unsuccessful, likely due to poor central nervous system (CNS) penetrance. Avapritinib novel CNS-penetrant PDGFRA/KIT inhibitor that FDA-approved for adults unresectable or...

Hypereosinophilic syndrome (HES) is a rare disorder characterized by persistent hypereosinophilia (HE) and organ dysfunction that occurs as a result of high levels of tissue eosinophil infiltration and/or extensive deposition of eosinophil-derived proteins. Because it is often difficult to make the differential diagnosis of HES despite conducting a careful evaluation, identifying particular pat...

A subset of GISTs lack mutations in the KIT/PDGFRA or RAS pathways and yet retain an intact succinate dehydrogensase (SDH) complex. We propose that these KIT/PDGFRA/SDH/RAS-P WT GIST tumors be designated as quadruple wild-type (WT) GIST. Further molecular and clinicophatological characterization of quadruple WT GIST will help to determine their prognosis as well as assist in the optimization of...

Multiple jejunalgastrointestinal stromal tumors (GISTs) were found in a 52-year-old woman with a history of neurofibromatosis type 1. These tumors were composed of interlacing fascicles of uniform spindle cells with eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for CD117, CD34 and negative for S-100, smooth muscle actin. Molecular analysis for activating mutations...

In the central nervous system (CNS), oligodendrocyte maturation and axonal myelination occur on a predictable schedule, but the underlying timing mechanisms are largely unknown. In the present study, we demonstrate that Nkx2.2 homeodomain transcription factor is a key regulator for the timing of oligodendrocyte differentiation during development. Whereas induced expression of Nkx2.2 in early ol...

Location 4q12 Protein Composed of an extracellular domain, a transmembrane domain, a juxtamembrane domain, and an intracellular domain; receptor tyrosine kinase; forms homodimer, and heterodimer with PDGFRB; dimerization induces kinase domain activation, leading to the activation of intracellular signalling pathways (Kawagishi et al., 1995). Somatic mutations Hybrid genes between various partne...

In 1998, gastrointestinal stromal tumor (GIST) emerged as a distinct oncogenetic entity and subsequently became a paradigm of targeted therapies in solid tumors. Diagnosis of GIST relies on both histology and immunohistochemistry. Ninety-five percent of GISTs express either KIT or DOG-1. Approximately 80%-90% of GISTs harbor gain-of-function mutations of either KIT or platelet-derived growth fa...

Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumors of the gastrointestinal tract, and most of them harbor KIT or platelet-derived growth factor receptor alpha (PDGFRA) gain-of-function mutations. Proper diagnostic assessment of GISTs has become very important since the availability of the molecular-targeted therapy with imatinib mesylate. Histopathology remai...

BACKGROUND The postulated relationship between KIT/PDGFRA mutations and their prognostic value in gastrointestinal stromal tumors (GISTs) has generated intense attention during the past decade, despite the fact that a great deal of studies have been conducted on this subject. To provide a strong quantitative estimate of this postulated relationship, we carried out a meta-analysis which combined...