KLF2

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.³ 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.

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

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence MZL gene
	2	relevance in PMBL/cHL/GZL not firmly established
	1-a	aSHM target and high-confidence DLBCL gene
	1-a	aSHM target and high-confidence FL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	8.60
DLBCL	Schmitz cohort	7.02
DLBCL	Reddy cohort	2.10
DLBCL	Chapuy cohort	2.99
FL	GAMBL genomes	2.31

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)
BL	Yes	No	2.274
DLBCL	Yes	No	3.067
FL	Yes	No	9.318

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

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

KLF2 Expression

References

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):830-7. doi: 10.1038/ng.892. PMID: 21804550; PMCID: PMC3297422.
Clipson, A., Wang, M., Leval, L., Ashton-Key, M., Wotherspoon, A., Vassiliou, G., Bolli, N., Grove, C., Moody, S., Escudero-Ibarz, L., Gundem, G., Brügger, K., Xue, X., Mi, E., Bench, A., Scott, M., Liu, H., Follows, G., Robles, E., Martinez-Climent, J., Oscier, D., Watkins, A., & Du, M. (2014). KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype. Leukemia, 29, 1177-1185. https://doi.org/10.1038/leu.2014.330.
Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, Wang JQ, Schmitz R, Morin RD, Tang J, Jiang A, Bagaev A, Plotnikova O, Kotlov N, Johnson CA, Wilson WH, Scott DW, Staudt LM. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer Cell. 2020 Apr 13;37(4):551-568.e14. doi: 10.1016/j.ccell.2020.03.015. PMID: 32289277; PMCID: PMC8459709.