Glioblastoma (GBM) is distinguished by a high degree of intratumoral heterogeneity, which extends to the pattern of expression and amplification of receptor tyrosine kinases (RTKs). Although most GBMs harbor RTK amplifications, clinical trials of small-molecule inhibitors targeting individual RTKs have been disappointing to date. Activation of multiple RTKs within individual GBMs provides a the...

Gastrointestinal stromal tumors (GISTs) are characterized by overexpression and mutations of c-Kit. Approximately 80% of c-Kit mutations occur in exon 11, being a response factor to imatinib (Gleevec) therapy. Mutations of platelet-derived growth factor receptor-alpha (PDGFRA) are observed in a subset of GISTs lacking c-Kit mutations.We aimed to assess whether c-Kit and PDGFRA mutation analysis...

Total anomalous pulmonary venous return (TAPVR) is a congenital heart defect inherited via complex genetic and/or environmental factors. We report detailed mapping in extended TAPVR kindreds and mutation analysis in TAPVR patients that implicate the PDGFRA gene in the development of TAPVR. Gene expression studies in mouse and chick embryos for both the Pdgfra receptor and its ligand Pdgf-a show...

Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized...

TO THE EDITOR The mitogen-activated protein kinase signaling pathway plays an important role in cell proliferation, differentiation and survival and is frequently altered in cancer. Genetic mechanisms that activate the mitogen-activated proteinkinase pathway vary among subtypes of melanoma when tumors are classified according to a combination of sun exposure and anatomic site (Maldonado et al.,...

Abstract Diffuse midline gliomas (DMG) are driven by self-renewing, stem-like glioma cells stalled in an oligodendrocyte precursor cell (OPC)-like state that characterized high expression of PDGFRA. This lineage overexpression PDGFRA, together with commonly found genomic amplifications and mutations has been shown to cooperate H3-K27M tumor development. Therefore, targeting PDGFRA long proposed...

Abstract Background TERT promoter (TERTp) mutations are a biological marker of glioblastoma; however, the prognostic significance TERTp mutational status is controversial. We evaluated this impact by retrospectively analyzing outcomes patients with isocitrate dehydrogenase (IDH)- and TERTp-wildtype glioblastomas. Methods Using custom next-generation sequencing, we analyzed 208 glioblastoma samp...

Cardiac sarcoma is a rare malignant tumor with undefined genetic mutations and no targeted therapy. Here in one rare case of undifferentiated cardiac intimal sarcoma (IS), a next-generation sequencing based assay, MSK-IMPACT (Memorial Sloan Kettering - Integrated Mutation Profiling of Actionable Cancer Targets), identified a somatic, activating mutation in PDGFRB, along with amplification of PD...

Myeloid and lymphoid neoplasms with PDGFRA gene rearrangements are a category of rare diseases that typically manifest with peripheral blood eosinophilia accompanied by eosinophilic tissue infiltrates, and may be associated with typical or atypical mast cell proliferations. These tumors can present as myeloproliferative neoplasms, acute myeloid leukemias or lymphoblastic leukemias/ lymphomas an...