The PDGFRA gene is located on the chromosome 4 in the region q12. It encodes an alpha subunit of the PDGF tyrosine kinase receptor, which (as well as the c-kit gene) belongs to the subgroup III of the protein tyrosine kinase family. The main function of the PDGFR protein is to mediate proliferation and differentiation of glia and mesenchymal cells.
In 2003, Heinrich et al. Found activating mutations in exons 12 and 18 of the PDGFRA gene in about of 35 % patients with gastrointestinal stromal tumors (GIST) in whom no mutation in the KIT gene was found.
As well as the already several times mentioned KIT protein, also the PRGFR protein, when in vitro, is selectively inhibited by imatinib mesylate (STI 571, Glivec). Information on the response to the treatment with Glivec in patients with GIST and with a mutation in the PDGFRA gene are so far just fragmentary and are the subject of further study.
In our laboratory, we perform the examination of the PDGFRA gene mutations in exons 12, 14 and 18 using PCR and direct sequencing.
Analytical sensitivity and specificity of the sequencing: 99%.
In the case of the analysis of somatic mutations by sequencing the mutations will not be detected, if the altered cell line is not represented by at least 20%.
- Kawagishi J, Kumabe T, Yoshimoto T, Yamamoto T. Structure, organization, and transcription units of the human alpha-platelet-derived growth factor receptor gene, PDGFRA. Genomics. 1995;30(2):224-32.
- Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299(5607):708-10.
- Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21(23):4342-9.
- Chompret A, Kannengiesser C, Barrois M, Terrier P, Dahan P, Tursz T, Lenoir GM, Bressac-De Paillerets B. PDGFRA germline mutation in a family with multiple cases of gastrointestinal stromal tumor. Gastroenterology. 2004 Jan;126(1):318-21.