PMS2 somatic loss-of-function in gastric produces dMMR/MSI-H phenotype. Pan- tumor MSI-H...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-PMS2-SOMATIC-GASTRIC |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-GASTRIC |
| Sources | SRC-ESMO-GASTRIC-2024 SRC-NCCN-GASTRIC-2025 |
Actionability Facts
| Biomarker | BIO-DMMR-IHC |
|---|---|
| Variant | PMS2 somatic loss-of-function (dMMR / MSI-H) |
| Disease | DIS-GASTRIC |
| ESCAT tier | IA |
| Recommended combinations | nivolumab + FOLFOX/CapeOX (1L MSI-H gastric, CheckMate-649), pembrolizumab + chemo (KEYNOTE-859), pembrolizumab monotherapy (pan-tumor MSI-H, 2L+) |
| Evidence summary | PMS2 somatic loss-of-function in gastric 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. 1L MSI-H gastric: nivolumab + chemo (CheckMate-649) and pembrolizumab + chemo (KEYNOTE-859) show enhanced benefit in MSI-H subgroup. Trastuzumab+pembro+chemo in HER2+ MSI-H (KEYNOTE-811). |
Notes
Somatic PMS2 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.