Variantes germinais SUFU patogênicas causam um Gorlin-síndrome – como predisposição com muito h...
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| ID | BMA-SUFU-GERMLINE-MEDULLOBLASTOMA |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-05-18 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-GBM |
| Fontes | SRC-NCCN-CNS-2025 |
Fatos de ação
| Biomarcador | BIO-SUFU-GERMLINE |
|---|---|
| Variante | Sufu patogênico da linha germinativa (similar ao NBCCS, meduloblastoma-predominante) |
| Doença | DIS-GBM |
| Nível ESCAT | IIA |
| Combinações recomendadas | brain MRI q4mo to age 3, q6mo to age 5, annual to age 8 — earlier and denser than PTCH1 cadence, dermatology surveillance q6-12mo from puberty, neurosurgery + COG-based protocols for medulloblastoma (avoid EBRT where alternatives available), do NOT default to vismodegib / sonidegib for SUFU-driven SHH-MB — downstream-of-SMO position renders SMO inhibition ineffective; consider GLI-pathway investigational agents in trial setting |
| Contraindicated monotherapy | vismodegib / sonidegib (SMO inhibitors) — limited efficacy in SUFU-mutant medulloblastoma; not a substitute for chemotherapy / radiation |
| Resumo das provas | SUFU germline pathogenic variants cause a Gorlin-syndrome–like predisposition with much higher medulloblastoma risk than PTCH1 (~30% lifetime vs ~5% in PTCH1), and lower BCC burden. SUFU-driven medulloblastomas cluster in the SHH-activated molecular subgroup (infant/young-child onset, desmoplastic / MBEN histology in many cases). Confirmed-carrier surveillance protocol (per Foulkes et al. 2017 / AACR Pediatric Predisposition Working Group): brain MRI q4mo from diagnosis through age 3, q6mo from age 3-5, annually to age 8 — denser-than-PTCH1 cadence reflects higher MB risk. Dermatology surveillance for BCC q6-12mo from puberty. Avoid craniospinal external-beam radiation when alternatives exist (second-malignancy risk in carriers). Hedgehog-pathway inhibitors (vismodegib, sonidegib) have limited activity in SUFU-mutant SHH-MB — downstream-of-SMO position renders SMO inhibitors ineffective; this is a critical distinction from PTCH1-driven disease. ESCAT IIA. |
Notas
STUB — Wave A+B germline expansion. Linked Indication: none (no SUFU-/Gorlin- specific Indication exists yet). Two-Clinical-Co-Lead signoff queued. Disease anchor uses DIS-GBM as closest CNS-tumor anchor; medulloblastoma lacks a Disease entity. The PTCH1-vs-SUFU distinction matters clinically: higher MB risk + tighter surveillance cadence + SMO-inhibitor resistance. Penetrance estimates remain unstable due to small published cohorts.
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