The PDGF receptor genes have also been found to be mutated in certain malignancies. Point mutations in the PDGFRα gene occur in about 5% of gastrointestinal stromal tumors (GIST); these mutations lead to amino acid residue replacements in critical regions of the receptor causing activation of the kinase. In GIST, similar mutations in the structurally related receptor Kit, is even more common. PDGF receptor genes have been found involved in gene rearrangements in certain leukemias. Thus, the intracellular parts of both PDGFRα and PDGFβ genes have been found to be fused to different partner genes that encode molecules that can oligomerize; the combination of loss of regulatory sequences in the juxtamembrane and transmembrane parts of the receptors and their oligomerization activate the receptor kinases. Moreover, in 5-10% of glioblastoma multiforme cases, the α-receptor gene is amplified resulting in expression of a high number of receptors. Amplification of PDGFRα has also been observed in oligodendrogliomas, esophageal squamous cell carcinoma, and artery intimal sarcomas. This makes the cells susceptible to stimulation by lowered amounts of PDGF, or if the number of receptors become high enough, signaling may occur in a PDGF-independent manner. An activating deletion mutation in the PDGFRα gene has also been detected in a human glioblastoma. Dysfunction of PDGF signaling, including PDGFRα, promotes the make difference in Brain tumors, Sarcomas, Leukemias and lymphomas, Prostate cancer, Liver cancer, Non-small cell lung cancer, Breast cancer, colon cancer and manu others
Heldin C-H. Targeting the PDGF signaling pathway in tumor treatment. Cell Communication and Signaling?: CCS. 2013;11:97.