MSH2 germline loss-of-function in ovarian 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-MSH2-GERMLINE-OVARIAN`
Type	Actionability
Status	reviewed 2026-04-27 \| pending_clinical_signoff \| actionability review required
Diseases	`DIS-OVARIAN`
Sources	`SRC-ESMO-OVARIAN-2024` `SRC-NCCN-OVARIAN-2025`

Actionability Facts

Biomarker	`BIO-DMMR-IHC`
Variant	MSH2 germline loss-of-function (dMMR / MSI-H)
Disease	`DIS-OVARIAN`
ESCAT tier	IA
Recommended combinations	pembrolizumab monotherapy (pan-tumor MSI-H/dMMR, FDA 2017), standard EOC therapy by HRD/BRCA status
Evidence summary	MSH2 germline loss-of-function in ovarian 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 is rare (~3%) in EOC; pembrolizumab tissue-agnostic applies in pretreated setting.

Notes

Germline MSH2 loss → cascade testing mandatory (Lynch syndrome). Family meets Amsterdam/Bethesda criteria. Pan-tumor MSI-H ICI eligibility supersedes tumor- specific lines.

Used By

No reverse references found in the YAML corpus.