Mutación activadora de PTPN11 (SHP2)
Vista determinista de la entidad fuente YAML. La autoridad clínica sigue con los ID de fuente citados y estado de firma del revisor.
| ID | BIO-PTPN11 |
|---|---|
| Tipo | Biomarcador |
| Aliaces | PTPN11 / mutación SHP2Активуюча мутація PTPN11 (SHP2) |
| Situación | reviewed 2026-05-04 | pending_clinical_signoff |
| Enfermedades | DIS-JMML |
| Fuentes | SRC-COG SRC-NCCN-AML-2025 |
Datos sobre biomarcadores
| Tipo de biomarcador | gene_mutation |
|---|---|
| Detalles de la mutación | {"exon": "3, 4, 8, 13 (dominios de EH2 y PTP)", "functional_impact":"activación", "gene": «PTPN11", "variant_type": „misense activación (E76K, D61G, Q79R, A72V, N308D más común)} |
| Medición | MétodoPanel NGS (tumor o gérmenes); puntos calientes comunes detectables en paneles hematológicos estándar |
| Consulta de la capacidad de acción | {"gene": "PTPN11", "variant": "activating_mutation"} |
| Productos químicos y químicos | BIO-KRAS-G12C BIO-KRAS-G12D |
Notas
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...
Utilizado por
Relevancia terapéutica
BMA-PTPN11-JMML- Las mutaciones somáticas de activación PTPN11 están presentes en ~35% de los casos de LMMJ y definen...
Enfermedad
DIS-JMML- Leucemia mielomonocítica juvenil (JMML)