PTPN11 activant la mutation (SHP2)
Vue déterministe de l'entité source de la LJAM. L'autorité clinique demeure avec les ID de la source cités et l'état d'approbation de l ́examinateur.
| ID | BIO-PTPN11 |
|---|---|
| Type | Biomarqueur |
| Alias | PTPN11 / mutation SHP2Активуюча мутація PTPN11 (SHP2) |
| État | reviewed 2026-05-04 | pending_clinical_signoff |
| Maladies | DIS-JMML |
| Sources | SRC-COG SRC-NCCN-AML-2025 |
Données biomarqueurs
| Type de biomarqueur | gene_mutation |
|---|---|
| Détails de la mutation | {"exon": "3, 4, 8, 13 (domaines de SH2 et PTP)", "functional_impact":"activation", "gene": «PTPN11", "variant_type":", "missense activation (E76K, D61G, Q79R, A72V, N308D le plus commun)} |
| Mesure | MéthodePanneaux NGS (tumoral ou germinatif); hotspots courants détectables sur des panneaux hématologiques standard |
| Recherche de la faisabilité | {"gene": "PTPN11", "variant": "activating_mutation"} |
| Biomarqueurs connexes | BIO-KRAS-G12C BIO-KRAS-G12D |
Notes
PTPN11 encodes SHP2, a protein tyrosine phosphatase that acts as a positive regulator of the RAS/MAPK pathway. Gain-of-function mutations disrupt autoinhibition, leading to constitutive RAS/ERK activation. Clinical contexts: (1) JMML: somatic PTPN11 mutations in ~35% — the single most common driver. Somatic PTPN11 in JMML carries poor prognosis; germline PTPN11 (Noonan syndrome) may cause a transient self-limiting myeloproliferative process that resolves without HCT. Critical to distinguish somatic vs germline origin — germline PTPN11 is a very different clinical entity. (2) Noonan syndrome (germline): most common cause (~50%); N308D, Q79R, D61G hotspots. Features: short stature, cardiac defects (pulmonary stenosis, HCM), webbed neck. Very low lifetime malignancy risk beyond juvenile myeloproliferative disease. (3) Acute leukemias: PTPN11 mutations in ~7% of AML, ~5% of B-ALL. (4) Solid tumors: ~5% of NSCLC, gastric, colorectal (often co-occurring with KRAS). Therapeutic target: SHP2 inhibitors are in active clinical development — TNO155 (Novartis), RMC-4630 (Revolution Medicines), ERAS-601 (Erasca). Phase I/II trials in solid tumors with KRAS mutations and PTPN11 mutations. SHP2...
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Pertinence thérapeutique
BMA-PTPN11-JMML- Les mutations somatiques d'activation du PTPN11 sont présentes dans environ 35 % des cas JMML et définissent...
Maladie
DIS-JMML- Leucémie myélomonocytique juvénile (JMML)