FOXL2 p.C134W mutation
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-FOXL2 |
|---|---|
| Type | Biomarker |
| Aliases | FOXL2 C134WМутація FOXL2 p.C134W |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESMO-OVARIAN-2024 SRC-NCCN-OVARIAN-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "1 (single exon gene)", "functional_impact": "dominant-negative / gain-of-function", "gene": "FOXL2", "hgvs_cdna": "c.402C>G", "hgvs_protein": "p.C134W", "variant_type": "missense"} |
| Measurement | MethodTumor NGS panel (DNA-based) or dedicated FOXL2 c.402C>G Sanger/ddPCR assay; highly recurrent hotspot |
| Actionability lookup | {"gene": "FOXL2", "variant": "C134W"} |
| Related biomarkers | None declared |
Notes
FOXL2 (Forkhead Box L2) is a transcription factor essential for granulosa cell differentiation and maintenance of ovarian identity. The p.C134W (c.402C>G) hotspot mutation is present in ~97% of adult granulosa cell tumors (AGCTs) and is the only known pathognomonic point mutation in any solid tumor (100% specificity if hotspot confirmed). The mutation is a dominant-negative gain-of-function: C134W FOXL2 protein mislocalizes and aberrantly activates target genes (including CYP19A1/aromatase), driving estrogen excess. Clinically, the mutation is used: (1) Diagnostic: confirms AGCT vs other sex cord-stromal tumors (Sertoli-Leydig, fibroma). (2) Prognostic/monitoring: ctDNA detection of FOXL2 c.402C>G for early relapse detection (AGCTs recur late — 10–20 years post-diagnosis; ctDNA surveillance under investigation). (3) Therapeutic target: FOXL2 inhibition and CDK4/6 inhibitors (olaparib, palbociclib, ribociclib) are in clinical trials. Luteinizing hormone-RH agonists (leuprolide) and progestins are used for recurrent disease but no FDA approval in this specific context. ESCAT IIB: clinically useful diagnostic marker with emerging predictive utility; no FDA-approved targeted drug for...
Used By
Actionability
BMA-FOXL2-GRANULOSA-CELL- FOXL2 p.C134W (c.402C>G) is the defining molecular marker of adult granulosa cell tumor (...
Diseases
DIS-GRANULOSA-CELL- Adult granulosa cell tumor of the ovary
Indications
IND-GRANULOSA-CELL-1L-CARBOPLATIN-PACLITAXEL- IND-GRANULOSA-CELL-1L-CARBOPLATIN-PACLITAXEL