Mutação de perda de função TSC1 (hamartin)
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| ID | BIO-TSC1 |
|---|---|
| Tipo | Biomarcador |
| Alegais | Mutação TSC1Мутація втрати функції TSC1 (гамартин) |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff |
| Doenças | DIS-LAM |
| Fontes | SRC-MILES-MCCORMACK-2011 SRC-NCCN-KIDNEY-2025 |
Fatos de biomarcadores
| Tipo de biomarcador | gene_mutation |
|---|---|
| Detalhes da mutação | {"exon": "multiple", "functional_impact":"perda de função", "gene": TSC1, "variant_type":", "perda da função (frameshift, absurdo, empilhagem, grande exclusão)} |
| Medição | MétodoGermline NGS panel (blood/saliva) for TSC diagnosis; tumor NGS for somatic TSC1/TSC2 in LAM/renal AML. TSC1 mutations less common than TSC2 in sporadic LAM (~10% vs ~80%). |
| Procura de ação | {"gene": "TSC1", "variant": "loss_of_function"} |
| Biomarcadores relacionados | Nenhuma declaração |
Notas
TSC1 (hamartin) forms a heterodimeric complex with TSC2 (tuberin) that acts as a GTPase activating protein (GAP) for Rheb, maintaining mTORC1 in an inactive state. Loss of either TSC1 or TSC2 → constitutive mTORC1 activation → protein synthesis, cell growth, proliferation. Clinical manifestations of TSC1 loss: (1) Tuberous Sclerosis Complex (TSC) — germline TSC1 (~30%) or TSC2 (~70%): cortical tubers, SEGA, renal AML, cardiac rhabdomyomas, LAM (females), skin lesions. TSC1 germline associated with milder phenotype than TSC2. (2) LAM — predominantly somatic TSC2 (>80%) or rarely TSC1 in sporadic LAM. TSC-associated LAM has germline TSC mutation. (3) Renal angiomyolipoma (sporadic) — somatic TSC1/TSC2 in ~50%. mTOR inhibitors (everolimus, sirolimus) are approved for multiple TSC/LAM manifestations: - Sirolimus: LAM (MILES 2011; FDA 2015) - Everolimus: SEGA (EXIST-1), renal AML (EXIST-2), TSC-related seizures (EXIST-3); renal cell carcinoma (SRC-BOLERO2-BASELGA-2012 — different indication via PIK3/AKT/mTOR pathway). Note: the BIO entity covers TSC1 specifically; TSC2 mutations are clinically similar but a separate gene — both treated with mTOR inhibitors.
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Relevância terapêutica
BMA-TSC1-LAM- Sirolimus (rapamycin), um mTORC1 inibidor, é FDA-aprovado (Maio) 2015) e EMA-aprovado (...BMA-TSC1-TSC-RENAL-AML- Everolimus (mTOR inhibitor) is FDA-approved (2012) for renal angiomyolipoma (AML) associa...
Doença
DIS-LAM- Linfangioleiomiomatose (LAM)
Indicação
IND-LAM-1L-SIROLIMUS- IND-LAM-1L-SIROLIMUS