🔍 Overview
The NF1 gene encodes neurofibromin, a tumor suppressor that functions as a Ras GTPase-activating protein (Ras-GAP) — it turns active Ras-GTP into inactive Ras-GDP, thus downregulating Ras signaling.
📊 Prevalence in Cancer
| Cancer Type | Frequency of NF1 Mutations |
|---|---|
| Neurofibromatosis type 1 | ~100% (germline mutation) |
| Malignant peripheral nerve sheath tumors (MPNST) | ~50% |
| Glioblastoma | ~10–15% |
| Lung adenocarcinoma | ~5–10% |
| Melanoma | ~5–15% |
| Breast cancer | ~3–5% |
⚙️ Mechanism of Tumorigenesis
- Loss-of-function mutations → Ras pathway hyperactivation.
- Leads to:
- Increased cell proliferation
- Survival signaling via MAPK and PI3K/AKT pathways
- Also associated with genomic instability.