Transformação em ativação do PTPN11 (SHP2)
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| ID | BIO-PTPN11 |
|---|---|
| Tipo | Biomarcador |
| Alegais | PTPN11 / mutação SHP2Активуюча мутація PTPN11 (SHP2) |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff |
| Doenças | DIS-JMML |
| Fontes | SRC-COG SRC-NCCN-AML-2025 |
Fatos de biomarcadores
| Tipo de biomarcador | gene_mutation |
|---|---|
| Detalhes da mutação | {"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)"} |
| Medição | MétodoPainel NGS (tumor ou linha germinativa); pontos-chave comuns detectáveis em painéis hematológicos padrão |
| Procura de ação | {"gene": "PTPN11", "variant": "activating_mutation"} |
| Biomarcadores relacionados | 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...
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Relevância terapêutica
BMA-PTPN11-JMML- As mutações somáticas de ativação PTPN11 estão presentes em ~35% dos casos de LMMJ e definem...
Doença
DIS-JMML- Leucemia mielomonocítica juvenil (JMML)