KLF2

Table of Contents

Overview
Relevance tier by entity
Mutation incidence in large patient cohorts (GAMBL reanalysis)
Mutation pattern and selective pressure estimates
aSHM regions
KLF2 Hotspots
Expression
References

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
	1	high-confidence MZL gene²
	2	relevance in PMBL/cHL/GZL not firmly established³
	1	aSHM target and high-confidence DLBCL gene¹
	1	aSHM target and high-confidence FL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

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Mutation pattern and selective pressure estimates

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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

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Expression

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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):830–837. PMCID: PMC3297422

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

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.