Table of Contents

Overview

KLF2 (Kruppel-like factor 2) is a transcription factor involved in the regulation of various cellular processes, including apoptosis, proliferation, and differentiation. Mutations in KLF2 have been identified in various B-cell lymphomas including DLBCL.1> KLF2 mutations are among the most common mutations in splenic marginal zone lymphoma (SMZL).2 KLF2 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. These mutations are associated with the BN2 genetic subgroup of DLBCL.1 KLF2 mutations have been shown to impair the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR, and TNFR signaling, thereby promoting lymphomagenesis. This implicates KLF2 as a tumor suppressor in B-cell lymphomas.2 Contradictory to this, the mutation pattern in DLBCL implies selective pressure to retain a full-length protein.

Relevance tier by entity

Entity Tier Description
DLBCL 1 High-confidence DLBCL gene
FL 2 Role of KLF2 mutations in FL requires confirmation
MZL 1 High-confidence MZL gene
PMBL 2 Role of KLF2 mutations in PMBL requires confirmation

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 57 0.0523 [0.0391,0.0656]
DLBCL GAMBL with Reddy 2,088 78 0.0374 [0.0292,0.0455]
DLBCL BC 231 15 0.0649 [0.0332,0.0967]
DLBCL Dana-Farber 303 7 0.0231 [0.0062,0.04]
DLBCL NCI 470 33 0.0702 [0.0471,0.0933]
DLBCL Reddy 999 21 0.0210 [0.0121,0.0299]
DLBCL DLBCL_ICGC 85 2 0.0235 [0,0.0558]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 11 0.0171 [0.0071,0.0272]
FL GAMBL with Crouch 1,189 27 0.0227 [0.0142,0.0312]
FL BC 379 8 0.0211 [0.0066,0.0356]
FL Kalmbach 164 1 0.0061 [0,0.018]
FL Crouch 547 16 0.0293 [0.0151,0.0434]
FL FL_ICGC 99 2 0.0202 [0,0.0479]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 2.1003 0.0000 1.0000
FL 3.1180 0.0000 1.0000
DLBCL 0.9739 2.6058 0.0661

aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chr19 16434978 16439011 TSS intron

KLF2 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr19 16436719 G>C K256N
chr19 16436723 A>G K258E
chr19 16436726 C>G R259G
chr19 16436726 C>T R259C
chr19 16436755 CA>TC T269P
chr19 16436769 C>T T273I
chr19 16436772 G>A C274Y
chr19 16436775 G>A S275N
chr19 16436775 G>C S275T
chr19 16436784 G>A G278D

Visualizations

Protein

View coding variants in ProteinPaint hg19 or hg38

Genome

View all variants in GenomePaint hg19 or hg38

Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2011-07-31 : Pasqualucci : DLBCL 2017-07-27 : Jallades : MZL 2019-08-20 : Desch : PMBL

References

1.
Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, Wells VA, Grunn A, Messina M, Elliot O, Chan J, Bhagat G, Chadburn A, Gaidano G, Mullighan CG, Rabadan R, Dalla-Favera R. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011 Jul 31;43(9):830–837. PMCID: PMC3297422
2.
Jallades L, Baseggio L, Sujobert P, Huet S, Chabane K, Callet-Bauchu E, Verney A, Hayette S, Desvignes JP, Salgado D, Levy N, Béroud C, Felman P, Berger F, Magaud JP, Genestier L, Salles G, Traverse-Glehen A. Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma. Haematologica. 2017 Oct;102(10):1758–1766. PMCID: PMC5622860
3.
Desch AK, Hartung K, Botzen A, Brobeil A, Rummel M, Kurch L, Georgi T, Jox T, Bielack S, Burdach S, Classen CF, Claviez A, Debatin KM, Ebinger M, Eggert A, Faber J, Flotho C, Frühwald M, Graf N, Jorch N, Kontny U, Kramm C, Kulozik A, Kühr J, Sykora KW, Metzler M, Müller HL, Nathrath M, Nüßlein T, Paulussen M, Pekrun A, Reinhardt D, Reinhard H, Rössig C, Sauerbrey A, Schlegel PG, Schneider DT, Scheurlen W, Schweigerer L, Simon T, Suttorp M, Vorwerk P, Schmitz R, Kluge R, Mauz-Körholz C, Körholz D, Gattenlöhner S, Bräuninger A. Genotyping circulating tumor DNA of pediatric Hodgkin lymphoma. Leukemia. 2020 Jan;34(1):151–166.

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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