SMARCB1 (INI1) loss of expression

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`BIO-SMARCB1`
Type	Biomarker
Aliases	SMARCB1/INI1 lossВтрата експресії SMARCB1 (INI1)
Status	reviewed 2026-05-04 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-ESMO-SARCOMA-2024` `SRC-EZH202-GOUNDER-2020` `SRC-NCCN-SARCOMA`

Biomarker Facts

Biomarker type	gene_mutation
Mutation details	{"exon": "multiple", "functional_impact": "loss-of-function", "gene": "SMARCB1", "variant_type": "biallelic inactivation (deletion, frameshift, nonsense; homozygous deletion common)"}
Measurement	MethodINI1/BAF47 IHC (loss of nuclear expression — standard clinical assay); NGS for mutation/deletion confirmation; FISH for homozygous 22q11 deletion
Actionability lookup	{"gene": "SMARCB1", "variant": "loss_of_function"}
Related biomarkers	None declared

Notes

SMARCB1 (INI1/hSNF5/BAF47) is a core subunit of the SWI/SNF chromatin remodeling complex. Biallelic inactivation removes SWI/SNF antagonism of EZH2 (PRC2 complex), leading to H3K27me3 accumulation and epigenetic silencing of tumor suppressor genes. This makes SMARCB1-deficient tumors selectively sensitive to EZH2 inhibition. SMARCB1 loss defines three main tumor types: (1) Epithelioid sarcoma — tazemetostat FDA-approved (2020; EZH-202 trial). (2) Malignant rhabdoid tumor (MRT, AT/RT in CNS) — extremely aggressive; no approved targeted therapy; investigational EZH2 inhibitors. (3) SMARCB1-deficient chordoma, sinonasal carcinoma — rare. IHC for INI1 (nuclear loss) is the companion diagnostic for tazemetostat in epithelioid sarcoma and is simpler than molecular testing. Note: retained INI1 expression does NOT exclude epithelioid sarcoma — ~10% of cases have normal INI1 by IHC despite molecular loss (technical or heterogeneous loss).

Used By

Actionability

BMA-SMARCB1-EPITHELIOID-SARCOMA - Tazemetostat (EPZ-6438), an EZH2 methyltransferase inhibitor, is FDA-approved (January 20...

Diseases

DIS-EPITHELIOID-SARCOMA - Epithelioid sarcoma

Indications

IND-EPITHELIOID-SARCOMA-1L-TAZEMETOSTAT - IND-EPITHELIOID-SARCOMA-1L-TAZEMETOSTAT