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Approximately 90% of GIST cases are associated with dysregulation of cell growth due to mutations of KIT and PDGFRA tyrosine kinases.
Additionally, the company has submitted a New Drug Application to the US Food and Drug Administration (FDA) for avapritinib for the treatment of adult patients with PDGFRA Exon 18 mutant GIST, regardless of prior therapy and fourth-line GIST.
Amplification of KIT, PDGFRA, VEGFR2, and EGFR in gliomas.
For locally advanced or metastatic GISTs, which are refractory to conventional radio- and chemotherapy, the discovery of the gain mutations regarding the KIT and PDGFRA genes has led to the use of adjuvant imatinib therapy.
In approximately 5% of cases, mutations are found in the homologous gene PDGFRA (platelet-derived growth factor receptor alpha).
Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations.
Finally, our results revealed that the expression of 01ig2 and PDGFRa markers (oligodendrocyte precursor markers) were higher in comparison to control group which is consistent with the results of immunocytochemistry (Figure 6).
Yao et al., "PDGFRa signaling drives adipose tissue fibrosis by targeting progenitor cell plasticity," Genes & Development, vol.
Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumor of the GI tract, mainly harbor a mutation of either the protooncogene KIT or the platelet-derived growth factor receptor alpha (PDGFRA) [1-3].
Mutational studies of platelet-derived growth factor receptor family of tyrosine kinases (PDGFRA) and tyrosine kinase receptor KIT (CD117) in Merkel cell carcinoma failed to demonstrate any activating mutations.
Separate from this classification, pathological conditions based on four molecular abnormalities, namely, PDGFRA, PDGFRbeta (PDGFRB), fibroblast growth factor receptor 1 (FGFR1), and PCM1JAK2 (fusion gene resulting from a t(8;9)(p22;p24) chromosomal translocation), are classified as myeloid/ lymphoid tumors, all of which belong to the HESN variant.
The molecular pathogenesis of these tumors includes gain-of-function mutations in C-kit and PDGFRA, which are both tyrosine kinase receptors.
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- PDGFA-Associated Protein 1
- PDGFRA/BCR fusion
- PDH complex
- PDH complex