diffuse large B-cell lymphoma germinal center B-cell type

disease

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Summary

diffuse large B-cell lymphoma germinal center B-cell type (MONDO:0850419) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 8 clinical trials. Molecularly, EZH2 expression confers sensitivity to Tazemetostat in Diffuse Large B-cell Lymphoma Germinal Center B-cell Type (CIViC Level C). Top therapeutic interventions include cyclophosphamide anhydrous, azacitidine, and belinostat.

At a glance

Classification: Cancer
Cohort genes: 1
Clinical trials: 8
Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	diffuse large B-cell lymphoma germinal center B-cell type
Mondo ID	MONDO:0850419
DOID	DOID:0080997
NCIT	C36080
UMLS	C1333295
MedGen	234202
GARD	0026615
Is cancer (heuristic)	yes

Data availability: 39 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › leukocyte disorder › B-cell neoplasm › neoplasm of mature B-cells › diffuse large B-cell lymphoma › diffuse large B-cell lymphoma germinal center B-cell type

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
EZH2	Act	ALL,AML,DLBCLNOS,ES,MLYM,NHL	CIViC #63

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EZH2	Orphanet:3447	Weaver syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EZH2	HGNC:3527	ENSG00000106462	Q15910	Histone-lysine N-methyltransferase EZH2	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EZH2	Histone-lysine N-methyltransferase EZH2	Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EZH2	Enzyme (other)	yes	2.1.1.356	SANT/Myb, SET_dom, EZH1/EZH2_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
embryo	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EZH2	216	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EZH2	9,646

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EZH2	Q15910	38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transcriptional Regulation by E2F6	1	292.8×	0.012	EZH2
Regulation of PTEN gene transcription	1	178.4×	0.012	EZH2
PKMTs methylate histone lysines	1	160.8×	0.012	EZH2
Defective pyroptosis	1	156.4×	0.012	EZH2
PRC2 methylates histones and DNA	1	152.3×	0.012	EZH2
Negative Regulation of CDH1 Gene Transcription	1	120.2×	0.012	EZH2
Regulation of PD-L1(CD274) transcription	1	108.8×	0.012	EZH2
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	91.4×	0.012	EZH2
Oxidative Stress Induced Senescence	1	90.6×	0.012	EZH2
HCMV Early Events	1	81.0×	0.012	EZH2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
hepatocyte homeostasis	1	8426.0×	0.002	EZH2
regulation of gliogenesis	1	5617.3×	0.002	EZH2
cellular response to trichostatin A	1	5617.3×	0.002	EZH2
negative regulation of striated muscle cell differentiation	1	4213.0×	0.002	EZH2
regulation of kidney development	1	4213.0×	0.002	EZH2
response to tetrachloromethane	1	4213.0×	0.002	EZH2
skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration	1	2808.7×	0.002	EZH2
cerebellar cortex development	1	2106.5×	0.002	EZH2
facultative heterochromatin formation	1	2106.5×	0.002	EZH2
regulatory ncRNA-mediated heterochromatin formation	1	1872.4×	0.002	EZH2
negative regulation of keratinocyte differentiation	1	1685.2×	0.002	EZH2
subtelomeric heterochromatin formation	1	1532.0×	0.002	EZH2
negative regulation of retinoic acid receptor signaling pathway	1	1532.0×	0.002	EZH2
G1 to G0 transition	1	1404.3×	0.002	EZH2
positive regulation of protein serine/threonine kinase activity	1	1296.3×	0.002	EZH2
positive regulation of cell cycle G1/S phase transition	1	1123.5×	0.003	EZH2
cardiac muscle hypertrophy in response to stress	1	1053.2×	0.003	EZH2
positive regulation of dendrite development	1	991.3×	0.003	EZH2
negative regulation of stem cell differentiation	1	842.6×	0.003	EZH2
negative regulation of transcription elongation by RNA polymerase II	1	766.0×	0.003	EZH2
positive regulation of MAP kinase activity	1	648.1×	0.003	EZH2
protein localization to chromatin	1	581.1×	0.004	EZH2
DNA methylation-dependent constitutive heterochromatin formation	1	543.6×	0.004	EZH2
liver regeneration	1	510.7×	0.004	EZH2
synaptic transmission, GABAergic	1	495.6×	0.004	EZH2
negative regulation of cytokine production involved in inflammatory response	1	421.3×	0.004	EZH2
negative regulation of gene expression, epigenetic	1	401.2×	0.004	EZH2
negative regulation of G1/S transition of mitotic cell cycle	1	358.6×	0.005	EZH2
positive regulation of epithelial to mesenchymal transition	1	318.0×	0.005	EZH2
stem cell differentiation	1	300.9×	0.005	EZH2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
EZH2	TAZEMETOSTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EZH2	6	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TAZEMETOSTAT	4	EZH2
MEVROMETOSTAT	2	EZH2
VALEMETOSTAT	2	EZH2
ZEPRUMETOSTAT	2	EZH2
GSK2816126	1	EZH2
CPI-1205	1	EZH2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
EZH2	839	Binding:833, Functional:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EZH2	2.1.1.356	[histone H3]-lysine27 N-trimethyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
EZH2	839

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

5 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
MEVROMETOSTAT	2	EZH2
VALEMETOSTAT	2	EZH2
ZEPRUMETOSTAT	2	EZH2
GSK2816126	1	EZH2
CPI-1205	1	EZH2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	EZH2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	3
PHASE1	3
PHASE2/PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04799275	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing CC-486 (Oral Azacitidine) Plus the Standard Drug Therapy in Patients 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma
NCT03038672	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas
NCT06649812	PHASE2	RECRUITING	Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
NCT06834373	PHASE2	RECRUITING	Golcadomide and Rituximab as Bridging Therapy for Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma Before CAR T-cell Therapy
NCT05627245	PHASE1	ACTIVE_NOT_RECRUITING	Testing the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment
NCT05755087	PHASE1	RECRUITING	Tegavivint for Treating Patients With Relapsed or Refractory Large B-Cell Lymphoma
NCT03742258	PHASE1	COMPLETED	Combination Chemotherapy and TAK-659 as Front-Line Treatment in Treating Patients With High-Risk Diffuse Large B Cell Lymphoma
NCT03656835	Not specified	ACTIVE_NOT_RECRUITING	Nanochip Technology in Monitoring Treatment Response and Detecting Relapse in Participants With Diffuse Large B-Cell Lymphoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	2
AZACITIDINE	4	1
BELINOSTAT	4	1
TAZEMETOSTAT	4	1
GOLCADOMIDE	3	1
TEGAVIVINT	2	1
VARLILUMAB	2	1
CHEMBL5398431	0	1
CHEMBL6083129	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
EZH2 expression	Tazemetostat	Sensitivity/Response	CIViC C	EID11108

Cohort genes: EZH2
Drugs: Cyclophosphamide, Azacitidine, Belinostat, Tazemetostat, Golcadomide