AIMS To assess the relation between KIT and PDGFRA mutations and the site of origin, histological phenotype, and pathomorphologically determined risk assessment in gastrointestinal stromal tumours (GISTs). METHODS A series of 83 clinicopathologically characterised GISTs from 79 patients was analysed for KIT and PDGFRA mutations by polymerase chain reaction amplification, single strand conform...

Schoppmann and colleagues (1) have recently investigated 174 gastrointestinal stromal tumor (GIST) by DNA array, FISH, exome sequencing, and immunohistochemistry (IHC) and found that the majority of recurrent chromosomal imbalances were located in 12 regions of interest and that the loss of 1p and immunohistochemical expressionof RAD54L2, SYNE2, KIT, andDIAPH1were associated with survival. In o...

in the present study, we investigated the association of PDGFRA and KIT mutations as well as PdGFra immunohistochemical expression with clinicopathologic features and prognosis in a series of gastrointestinal stromal tumors (GiSTs). Tumor dna from 40 GiSTs was sequenced for the presence of mutations in KIT exons 9, 11, 13 and 17, and in PDGFRA exons 12 and 18. Tissue sections were stained with ...

Lartruvo (olaratumab) is a monoclonal antibody against the extracellular domain of PDGFRA. Olaratumab blocks ligand binding and thereby inhibits activation of PDGFRA kinase activity. Pre-clinically, this antibody inhibited PDGFRA-dependent tumor growth. In a randomized Phase II study, adding olaratumab to doxorubicin chemotherapy significantly improved overall survival, leading to FDA approval.

PURPOSE Inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer due to its rapid onset and highly invasive nature. IBC carries 5- and 10-year disease-free survival rates of ~45% and <20%, respectively. Multiple studies demonstrate that in comparison with conventional breast cancer, IBC has a unique molecular identity. Here, we have identified platelet-derived growth fac...

KIT expression is a key diagnostic feature of gastrointestinal stromal tumors (GISTs), and virtually all of the GISTs express oncogenic forms of the KIT or PDGFRA receptor tyrosine kinase proteins, which serve as therapeutic targets of imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). However, KIT expression can be low in PDGFRA-mutant GISTs, increasing the likelihood of misdiagnosis a...

A novel oncogenic mutation (FIP1L1-PDGFRA), which results in a constitutively activated platelet-derived growth factor receptor-alpha (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 co...

Cardiac development in vertebrates is a finely tuned process regulated by a set of conserved signaling pathways. Perturbations of these processes are often associated with congenital cardiac malformations. Platelet-derived growth factor receptor α (PDGFRα) is a highly conserved tyrosine kinase receptor, which is essential for development and organogenesis. Disruption of Pdgfrα function in murin...

The FIP1L1-PDGFRA rearrangement results in constitutive activation of the tyrosine kinase PDGFRA. Neoplasms harboring this rearrangement are responsive to imatinib mesylate at doses much lower than those recommended for the treatment of chronic myelogenous leukemia. Only a single report has described the identification of FIP1L1-PDGFRA in chronic myelomonocytic leukemia (CMML). Herein, we prese...

Abstract Gastrointestinal stromal tumors (GIST) harboring activating mutations of PDGFRA respond to imatinib, with the notable exception most common mutation, D842V. Avapritinib is a novel, potent KIT/PDGFRA inhibitor substantial clinical activity in patients D842V genotype. To date, only minority PDGFRA-mutant treated avapritinib have developed secondary resistance. Tumor and plasma biopsies 6...