PDGFRA
🔍 What is PDGFRA?
PDGFRA encodes a receptor tyrosine kinase that binds platelet-derived growth factors (PDGFs). It plays a key role in regulating cell growth, development, and survival. Mutations in PDGFRA can lead to constitutive activation of the receptor, driving oncogenesis.
📊 Prevalence of PDGFRA Alterations in Cancer
| Cancer Type | Frequency of PDGFRA Alterations |
|---|---|
| Gastrointestinal stromal tumors (GIST) | ~5-10% (less common than KIT mutations) |
| Gliomas | Rare, but can have PDGFRA amplifications or mutations |
| Other sarcomas | Occasional PDGFRA involvement |
⚙️ Mechanism of Oncogenic Activation
- PDGFRA mutations commonly occur in:
- Exon 18 (kinase domain, including the D842V mutation)
- Exons 12 and 14 (juxtamembrane and kinase domains)
- Constitutive activation leads to downstream signaling through:
- RAS-RAF-MEK-ERK (MAPK) pathway
- PI3K-AKT-mTOR pathway
- STAT pathway
- This causes uncontrolled cell proliferation and survival.