IL4R

Table of Contents

Overview
Relevance tier by entity
Mutation incidence in large patient cohorts (GAMBL reanalysis)
Mutation pattern and selective pressure estimates
aSHM regions
IL4R Hotspots
Expression
References

Overview

Mutations in IL4R have been identified in various types of B-cell lymphomas, particularly primary mediastinal large B-cell lymphoma (PMBCL) and DLBCL. IL4R 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. IL4R mutations are found in approximately 24.2% of primary PMBCL cases. These mutations are commonly single nucleotide variants in exon 8, resulting in the I242N amino acid change. This leads to constitutive activation of the JAK-STAT signaling pathway and upregulation of downstream cytokine expression profiles and B cell-specific antigens.^1,2 In DLBCL, IL4R mutations are more rare and tend to occur within the GCB subgroup.²

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene¹
	1	aSHM target and high-confidence DLBCL gene²

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
chr16	27322895	27329423	TSS	active_promoter

IL4R Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr16	27367183	T>A	I242N

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Expression

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References

Viganò E, Gunawardana J, Mottok A, Van Tol T, Mak K, Chan FC, Chong L, Chavez E, Woolcock B, Takata K, Twa D, Shulha HP, Telenius A, Kutovaya O, Hung SS, Healy S, Ben-Neriah S, Leroy K, Gaulard P, Diepstra A, Kridel R, Savage KJ, Rimsza L, Gascoyne R, Steidl C. Somatic IL4R mutations in primary mediastinal large B-cell lymphoma lead to constitutive JAK-STAT signaling activation. Blood. 2018 May 3;131(18):2036–2046.

Duns G, Viganò E, Ennishi D, Sarkozy C, Hung SS, Chavez E, Takata K, Rushton C, Jiang A, Ben-Neriah S, Woolcock BW, Slack GW, Hsi ED, Craig JW, Hilton LK, Shah SP, Farinha P, Mottok A, Gascoyne RD, Morin RD, Savage KJ, Scott DW, Steidl C. Characterization of DLBCL with a PMBL gene expression signature. Blood. 2021 Jul 15;138(2):136–148.