CREBBP

Overview

CREBBP mutations are highly prevalent in both DLBCL and FL.pasqualucciInactivatingMutationsAcetyltransferase2011a? These mutations often affect the histone acetyltransferase (HAT) domain, crucial for regulating gene expression through chromatin modification, or generate a truncated protein.pasqualucciInactivatingMutationsAcetyltransferase2011a? This gene has some recurrent sites of mutations (hotspots), mostly in the HAT domain. The pattern of mutations in DLBCL is distinct from FL with the latter having more HAT domain mutations relative to truncating mutations.1

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2011-03-10 : Pasqualucci : DLBCL 2012-12-01 : Love : BL 2013-12-13 : Parry : MZL 2021-07-15 : Duns : PMBL

Relevance tier by entity

Entity Tier Description
MZL 2 relevance in MZL not firmly established2
PMBL 1 high-confidence PMBL/cHL/GZL genedunsCharacterizationDLBCLPMBL2021b?
DLBCL 1 high-confidence DLBCL genepasqualucciInactivatingMutationsAcetyltransferase2011a?
FL 1 high-confidence FL genepasqualucciInactivatingMutationsAcetyltransferase2011a?
BL 2 association with BL is tenuous3

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity source frequency (%)
DLBCL GAMBL genomes 25.81
DLBCL Schmitz cohort 17.87
DLBCL Reddy cohort 12.11
DLBCL Chapuy cohort 16.67
FL GAMBL genomes 65.13
BL GAMBL genomes+capture 6.00
BL Thomas cohort 3.00
BL Panea cohort 12.90

Mutation pattern and selective pressure estimates

Entity aSHM Significant selection dN/dS (missense) dN/dS (nonsense)
BL No No 1.357 3.999
DLBCL No Yes 13.231 65.302
FL No Yes 43.869 112.938

CREBBP Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr16 3788618 G>A R1446C
chr16 3788617 C>T R1446H
chr16 3788617 C>A R1446L
chr16 3788606 A>T Y1450N
chr16 3788606 A>C Y1450D
chr16 3788605 T>G Y1450S
chr16 3788605 T>C Y1450C
chr16 3788596 A>G I1453T
chr16 3788594 G>T L1454I
chr16 3788593 A>C L1454R
chr16 3786715 A>T L1499Q
chr16 3786715 A>G L1499P
chr16 3786715 A>C L1499R
chr16 3786710 C>A E1501*
chr16 3786707 A>T W1502R
chr16 3786707 A>G W1502R
chr16 3786705 C>T W1502*
chr16 3786705 C>G W1502C
chr16 3786705 C>A W1502C
chr16 3786704 A>T Y1503N
chr16 3786704 A>G Y1503H
chr16 3786704 A>C Y1503D
chr16 3786703 T>G Y1503S
chr16 3786703 T>A Y1503F
chr16 3786691 A>G L1507P

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

CREBBP Expression

Representative Mutations

BL3

Rating ★ ★ ★ ★ ☆

All Mutations

BL

1093 322 324 515 677 745 851

References

1.
Dreval K, Hilton LK, Cruz M, Shaalan H, Ben-Neriah S, Boyle M, Collinge B, Coyle KM, Duns G, Farinha P, Grande BM, Meissner B, Pararajalingam P, Rushton CK, Slack GW, Wong J, Mungall AJ, Marra MA, Connors JM, Steidl C, Scott DW, Morin RD. Genetic subdivisions of follicular lymphoma defined by distinct coding and noncoding mutation patterns. Blood. 2023 Aug 10;142(6):561–573. PMCID: PMC10644066
2.
Parry M, Rose-Zerilli MJJ, Gibson J, Ennis S, Walewska R, Forster J, Parker H, Davis Z, Gardiner A, Collins A, Oscier DG, Strefford JC. Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma. PLoS One. 2013;8(12):e83244. PMCID: PMC3862727
3.
Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, Richards KL, Dunphy CH, Choi WWL, Srivastava G, Lugar PL, Rizzieri DA, Lagoo AS, Bernal-Mizrachi L, Mann KP, Flowers CR, Naresh KN, Evens AM, Chadburn A, Gordon LI, Czader MB, Gill JI, Hsi ED, Greenough A, Moffitt AB, McKinney M, Banerjee A, Grubor V, Levy S, Dunson DB, Dave SS. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012 Dec;44(12):1321–1325. PMCID: PMC3674561

Citing

If you use the information or data from this site, please cite

Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.

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