CREBBP

Overview

CREBBP encodes a histone acetyltransferase and transcriptional coactivator. In the cbio-kb corpus it appears as a relapse-associated epigenetic regulator in MLL-rearranged acute lymphoblastic leukemia PMID:25730765.

Alterations observed in the corpus

  • Point mutations identified in relapse samples of infant MLL-rearranged ALL, consistent with a role in treatment resistance PMID:25730765.
  • Mutations in epigenetic regulators including CREBBP were frequent (45%) in older children with MLL-R leukemia but rare in infants PMID:25730765.
  • Subthreshold recurrent inactivating mutations in meningioma (q = 0.126); enriched in MG3/MG4 high-risk molecular groups in an integrative molecular classification of 565 meningiomas PMID:34433969.
  • CREBBP alterations were found almost exclusively in the other-MAPK-mutant subtype of PDAC (P = 1.3 × 10⁻⁵ vs KRAS-mutant; 0% in MAPK-WT) in the 2,336-patient pdac_msk_2024 cohort, associating CREBBP mutation with the non-KRAS-driven MAPK subtype PMID:39753968.
  • Shared trunk mutation identified in phylogenetic analyses of bladder cancer primary-metastasis pairs PMID:36543146
  • CREBBP is a chromatin-modifying gene with high prevalence of non-silent variants in metastatic UC (UC-GENOME cohort) PMID:36333289
  • Identified as somatically mutated in HGSOC in TCGA integrated genomic analysis of ovarian carcinoma PMID:21720365
  • Identified as recurrently mutated in DLBCL and FL by whole-genome/exome sequencing of non-Hodgkin lymphomas PMID:21796119
  • Identified as a recurrently mutated gene in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing of 55 tumors PMID:22343534
  • Found mutated in medulloblastoma WGS cohort (PCGP, 37 tumors), supporting a role for chromatin remodeling gene disruption in pediatric medulloblastoma PMID:22722829
  • Mutated in TCGA lung squamous cell carcinoma cohort (178 tumors) PMID:22960745
  • Mutated in SCLC WES/WGS study (CLCGP, 29 tumors) PMID:22941188
  • Mutated in ALL (St. Jude WGS/WES, 44 tumors); CREBBP mutations identified as recurrent alterations, disrupting transcriptional coactivator function and histone acetylation in pediatric acute lymphoblastic leukemia PMID:23334668
  • KAT11 domain missense mutations (R1446C, I1453N, W1472S) in 7% of ACC WES cohort (n=60); histone acetyltransferase designated CHASM driver PMID:23685749
  • Missense p.R1446C in the KAT11 domain in ACC; part of chromatin-remodeling gene cluster collectively 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
  • Single frameshift mutation p.Pro830LeufsTer19 in sinonasal AdCC (1/21 sequenced cases); part of the long tail of singleton mutations PMID:24418857
  • Significantly mutated histone acetyltransferase in muscle-invasive bladder carcinoma (BLCA); focal deletions targeting CREBBP identified by GISTIC 2.0; part of the 76% of tumours with inactivating chromatin regulator mutations PMID:24476821
  • Truncating mutations in 13% of muscle-invasive urothelial carcinoma; mutually exclusive with EP300 truncating mutations (15%); both are chromatin modifier genes with HAT activity PMID:25092538
  • Chromatin remodeler truncated in cutaneous squamous cell carcinoma; truncating CREBBP and EP300 events are mutually exclusive with NOTCH truncations in 29-tumor 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 (CREBBP) found in both low- and high-grade UTUC; concordant across spatial tumor components suggesting early/clonal events PMID:26278805
  • Loss-of-function mutations (p.Gln839* nonsense, p.Ser1207fs frameshift) in the histone acetyltransferase domain in CTCL (Sézary syndrome) PMID:26551667
  • Only mouse-model gCIS (genome-wide common insertion site) observed across all compartments (primary + local + metastatic recurrence) in Shh medulloblastoma PMID:26760213
  • CREBBP identified among epigenetic regulator mutations in PDTC/ATC thyroid tumors (IMPACT 341-gene panel, 117 tumors); listed alongside EP300, BCOR, BCL6 as other epigenetic regulators recurrently altered in ATC PMID:26878173
  • CREBBP was identified in the Pan-Lung analysis as part of the EP300/CREBBP HAT-domain hotspot region (additional significantly mutated gene); CREBBP focal deletions were found in lung SqCC PMID:27158780.
  • CREBBP — chromatin modifier enriched among unmet medical need (UMD) LUAD patients, particularly in never/former-light smokers; co-occurs with KMT2D, KMT2C, and SETD2 as a cluster of epigenetic alterations in this subset PMID:28336552
  • Recurrent HAT-complex alteration in medulloblastoma, predominantly in SHH subgroup (HAT complex genes collectively altered in 19% of SHH MBs); found alongside EP300, KAT6B, BRPF1, and KANSL1 PMID:28726821.
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Cancer types (linked)

  • BLLKMT2A: CREBBP mutations observed at relapse in infant MLL-R ALL PMID:25730765.
  • MNG: Subthreshold recurrent inactivating mutations enriched in MG3/MG4 meningioma groups; may contribute to epigenetic dysregulation driving aggressive behavior PMID:34433969.
  • PAAD: CREBBP alterations specific to the other-MAPK-mutant PDAC subtype (P = 1.3 × 10⁻⁵ vs KRAS-mutant) in the 2,336-patient pdac_msk_2024 cohort PMID:39753968.

Co-occurrence and mutual exclusivity

  • Not reported in this corpus.

Therapeutic relevance

  • Not reported in this corpus.

Open questions

  • Whether CREBBP relapse mutations are selected by therapy or pre-existing sub-clones PMID:25730765.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36543146

This page was processed by crosslinker on 2026-05-14. - PMID:36333289

This page was processed by crosslinker on 2026-05-14. - PMID:21720365

This page was processed by crosslinker on 2026-05-14. - PMID:21796119

This page was processed by crosslinker on 2026-05-14. - PMID:22343534

This page was processed by crosslinker on 2026-05-14. - PMID:22722829

This page was processed by crosslinker on 2026-05-14. - PMID:22960745

This page was processed by crosslinker on 2026-05-14. - PMID:22941188

This page was processed by crosslinker on 2026-05-14. - PMID:23334668

This page was processed by crosslinker on 2026-05-14. - PMID:23685749

This page was processed by crosslinker on 2026-05-14. - PMID:23778141

This page was processed by crosslinker on 2026-05-14. - PMID:24121792

This page was processed by crosslinker on 2026-05-14. - PMID:24418857

This page was processed by crosslinker on 2026-05-14. - PMID:24476821

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:26551667

This page was processed by wiki-cli on 2026-05-14. - PMID:26760213

This page was processed by wiki-cli on 2026-05-14. - PMID:26878173

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

This page was processed by wiki-cli on 2026-05-14. - PMID:28336552

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:28985567

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

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