EP300

Overview

EP300 (E1A Binding Protein P300) is a histone acetyltransferase and transcriptional co-activator. EP300 is a chromatin-modifying gene frequently mutated in urothelial carcinoma.

Alterations observed in the corpus

• Chromatin-modifying gene with high prevalence of non-silent variants in metastatic urothelial carcinoma (UC-GENOME cohort), consistent with TCGA-BLCA PMID:36333289
• EP300 was identified as a recurrently mutated gene in DLBCL and FL, implicating histone acetyltransferase activity in lymphomagenesis PMID:21796119
• Inactivating mutations in HAT domain in SCLC (29 tumors, CLCGP WES/WGS); mutually exclusive with CREBBP alterations PMID:22941188
• Hotspot mutations in chromatin-modifying gene in SCLC (36 tumors, JHU WES/WGS) PMID:22941189
• Splice-site mutation in the KAT11 acetyltransferase domain (G1429_splice) identified in adenoid cystic carcinoma (ACC); functions as a CREBBP co-activator PMID:23685749
• Mutated (along with CREBBP p.R1446C in the KAT11 domain) in adenoid cystic carcinoma; part of a chromatin-remodeling gene cluster mutated in 12/24 cases PMID:23778141
• Mutation in bladder TCC as part of a chromatin-remodeling gene cluster altered in 58% of cases PMID:24121792
• EP300 mutated in 3/21 (14%) of sinonasal adenoid cystic carcinoma cases, with frameshift (c.3355del p.Asp1119MetfsTer38), missense (c.1811G>A p.Arg604Gln), and nonsense (c.1927G>T p.Glu643Ter) variants PMID:24418857
• EP300 identified as a significantly mutated histone acetyltransferase in 15% of muscle-invasive bladder cancers; chromatin-targeting therapies proposed for the 76% of tumors with chromatin regulator mutations including EP300 PMID:24476821
• Phosphorylated at S1834 downstream of SEMA7A/ITGB1/AKT signaling in GBC cells; p300-S1834 phosphorylation drives H3K27ac at SNAI1 and ZEB1 promoters promoting EMT; S1834A mutant is null; the AKT→EP300 axis proposed as a therapeutic target in GBC PMID:24997986
• Truncating mutations in 15% of muscle-invasive bladder cancer (MSKCC cohort); mutually exclusive with CREBBP truncating mutations (13%) PMID:25092538
• Truncating EP300 mutations in cSCC; EP300 truncating events are mutually exclusive with NOTCH truncating events; EP300 is a chromatin remodeler truncated or hit at COSMIC sites in 48% of the cSCC cohort PMID:25589618
• Clustered mutations and recurrent inactivating translocations in SCLC (110-tumour WGS cohort); not significantly associated with overall survival PMID:26168399
• Chromatin-modifier mutations (EP300) found in both low- and high-grade UTUC; concordant across spatial tumor components suggesting early/clonal events PMID:26278805
• Hypothesized to acetylate FOXA1 at K264/K267/K270 in the W2 domain; FOXA1 W2 hotspot mutations in ILC may alter EP300-dependent acetylation (mechanistic hypothesis, not directly tested) PMID:26451490
• Mentioned in study PMID:26862087
• EP300 mutations are among the epigenetic-regulator alterations detected in advanced thyroid cancers (PDTC/ATC) profiled by MSK-IMPACT 341-gene panel; EP300 alterations co-occur with other chromatin-modifier mutations enriched in the ATC histology PMID:26878173
• Identified as part of the recurrently mutated chromatin-modifier landscape in the TCGA pan-lung cancer cohort PMID:27158780
• EP300 identified as a tumor-suppressor/chromatin alteration flagged as actionable in a genomic profiling study of cisplatin-resistant germ cell tumors (GCT) using targeted sequencing PMID:27646943
• Recurrent HAT-complex alteration in medulloblastoma, predominantly in SHH subgroup (HAT complex genes collectively altered in 19% of SHH MBs); found alongside CREBBP, KAT6B, BRPF1, and KANSL1 PMID:28726821.
• Epigenetic regulator identified as a truncal or subclonal event in matched-tumor phylogenetic analysis of prostate cancer across disease states (locoregional to mCRPC) in the SU2C/PCF cohort PMID:28825054.
• Histone acetylase chromatin-modifier SMG in MIBC; predominantly inactivating mutations; grouped with other chromatin-modifier SMGs (CREBBP, KMT2C, KMT2A, KMT2D, KDM6A, ARID1A, ASXL1, ASXL2) in the TCGA 2017 MIBC analysis PMID:28988769

Cancer types (linked)

• Urothelial carcinoma (UC): recurrently mutated chromatin modifier PMID:36333289

Co-occurrence and mutual exclusivity

• Frequently co-mutated with other chromatin-modifying genes (KMT2D, ARID1A, KDM6A, KMT2C, KMT2A, CREBBP, SMARCA4) in metastatic UC PMID:36333289

Therapeutic relevance

Open questions

Sources

• PMID:36333289

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This page was processed by crosslinker on 2026-05-14. - PMID:25092538

This page was processed by crosslinker on 2026-05-14. - PMID:25589618

This page was processed by crosslinker on 2026-05-14. - PMID:26168399

This page was processed by crosslinker on 2026-05-14. - PMID:26278805

This page was processed by crosslinker on 2026-05-14. - PMID:26451490

This page was processed by crosslinker on 2026-05-14. - PMID:26862087

This page was processed by entity-page-writer on 2026-05-15. - PMID:26878173

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27646943

This page was processed by entity-page-writer on 2026-05-15. - PMID:28726821

This page was processed by wiki-cli on 2026-05-15. - PMID:28825054

This page was processed by wiki-cli on 2026-05-15. - PMID:28988769

This page was processed by wiki-cli on 2026-05-15.