MSH6 somatic loss-of-function in urothelial produces dMMR/MSI-H phenotype. Pan-tumor MSI-...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-MSH6-SOMATIC-UROTHELIAL |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-UROTHELIAL |
| Sources | SRC-CIVIC SRC-EAU-PROSTATE-2024 SRC-NCCN-BLADDER-2025 |
Actionability Facts
| Biomarker | BIO-DMMR-IHC |
|---|---|
| Variant | MSH6 somatic loss-of-function (dMMR / MSI-H) |
| Disease | DIS-UROTHELIAL |
| ESCAT tier | IB |
| Recommended combinations | pembrolizumab monotherapy (pan-tumor MSI-H, FDA 2017), standard urothelial therapy (cisplatin or ICI 1L per PD-L1) |
| Evidence summary | MSH6 somatic loss-of-function in urothelial produces dMMR/MSI-H phenotype. Pan-tumor MSI-H ICI eligibility (pembrolizumab per KEYNOTE-158, dostarlimab per GARNET) supersedes tumor-specific lines via tissue-agnostic FDA approval. MSI-H in urothelial is rare (~3-5%); pembrolizumab tissue-agnostic applies. |
Notes
Somatic MSH6 loss → cascade testing optional (reflex germline confirmation strongly recommended; ~30% of dMMR tumors have germline cause). Pan-tumor MSI-H ICI eligibility supersedes tumor-specific lines.
Used By
No reverse references found in the YAML corpus.