PDGFRA codon(s) 842 any
|Tumor(s)||Gastrointestinal Stromal Tumor|
The D842V mutation results in an amino acid substitution at position 842 in PDGFRA, from an aspartic acid (D) to a valine (V). This mutation occurs within the TK2 domain. PDGFRA D842V mutation has been found in a distinct subset of GIST, typically from the stomach. The D842V mutation is known to be associated with tyrosine kinase inhibitor resistance. Recent evidence has shown that Dasatinib has been also recently associated with promising clinical activity in patients with advanced GIST carrying exon 18 mutation of the PDGFRA gene (including the D842V mutation). Interestingly, recent in vitro data have suggested that crenolanib, a highly selective and potent inhibitor of both PDGFRA and PDGFRB, blocks phosphorylation of D842V mutant PDGFRA at clinically achievable concentrations
Corless et al.. PDGFRA Mutations in Gastrointestinal Stromal Tumors: Frequency, Spectrum and In Vitro Sensitivity to Imatinib. 2005 J Clin Oncol 23:5357-5364.
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