PDGFR and Human Cancer
PDGF activated pathways play a central role in a number of human malignancies either through its translocation, amplification and activation point mutation and/or over expression of its receptors or ligands.
Dermatofibrosarcoma protuberans (DFSP) is caused dues to translocation of the PDGFB gene to the COL1A1 gene.
- High grade pediatric gliomas are associated with amplification of the PDGFRA gene which composes of 5% - 25%.
- Some gliomas are found to have a deletion mutant of the PDGFRA which is continuously active.
- 5%-12% of the Gastrointestinal stromal tumors (GIST) are caused due to activating point mutations and small deletions in the PDGFRA gene.
- Mutationally caused changes causes over expression of PDGFRA in Lung carcinoma (3%-4%).
- Idiopathic hypereosinophilic syndrome (IHES) is caused due to fusion of PDGFRA gene with the genes for FIP1L1, K1F5B, or CDKRAP2 in approximately 10%-30% of the cases.
- Exon 12 mutations of PDGFRA are responsible for Inflammatory fibroid polyps which represent polypous proliferations of spindle cells in the submucosa and mucosa of the stomach, small bowel and colon with inflammatory infiltration.
Chronic myelomonocytic leukemia (CMML) is also caused due to fusion of PDGFRB gene with the TEL gene in approximately 30% of the cases.