PTPN11-Aktivierungsmutation (SHP2)
Deterministische Ansicht der Quelle YAML Entität. Klinische Autorität bleibt mit den zitierten Quell-IDs und Rezensenten Sign-off Zustand.
| ID | BIO-PTPN11 |
|---|---|
| Art | Biomarker |
| Aliase | PTPN11 / SHP2-MutationАктивуюча мутація PTPN11 (SHP2) |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Erkrankungen | DIS-JMML |
| Quellen | SRC-COG SRC-NCCN-AML-2025 |
Biomarker-Fakten
| Biomarker-Typ | gene_mutation |
|---|---|
| Angaben zur Mutation | {"exon": "3, 4, 8, 13 (SH2 and PTP domains)", "functional_impact": "activating", "gene": "PTPN11", "variant_type": "missense activating (E76K, D61G, Q79R, A72V, N308D most common)"} |
| Messung | VerfahrenNGS-Panel (Tumor oder Keimlinie); gemeinsame Hotspots auf Standard-hämatologischen Panels nachweisbar |
| Nachschlagewerk für die Aktionsfähigkeit | {"gene": "PTPN11", "variant": "activating_mutation"} |
| Verwandte Biomarker | BIO-KRAS-G12C BIO-KRAS-G12D |
Anmerkungen
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...
Verwendet von
Therapeutische Relevanz
BMA-PTPN11-JMML- PTPN11 somatische aktivierende Mutationen sind in ~35% der JMML-Fälle vorhanden und definieren die...
Erkrankung
DIS-JMML- Juvenile myelomonozytäre Leukämie (JMML)