NFKBIZ

Overview

The NFKBIZ gene is a significant player in NF-κB signaling, with mutations leading to its deregulation. This pathway is critical in the pathogenesis of ABC DLBCL. NFKBIZ 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. The predominant cluster of mutations in NFKBIZ is in the 3’ UTR and not a consequence of aSHM. NFKBIZ 3’ UTR mutations confer a selective growth advantage in DLBCL cells by stabilizing NFKBIZ mRNA, resulting in increased protein levels.¹

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2016-05-01 : Morin : DLBCL

Relevance tier by entity

Entity	Tier	Description
	1-a	aSHM target and high-confidence DLBCL gene²

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	1.53
DLBCL	Schmitz cohort	1.28
DLBCL	Reddy cohort	1.50
DLBCL	Chapuy cohort	0.85

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)
BL	Yes	No	3.346
DLBCL	Yes	No	2.091
FL	Yes	No	0.000

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr3	101546669	101547704	TSS-1	active_promoter
chr3	101568239	101569274	TSS-2	active_promoter

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

NFKBIZ Expression

References

Arthur SE, Jiang A, Grande BM, Alcaide M, Cojocaru R, Rushton CK, Mottok A, Hilton LK, Lat PK, Zhao EY, Culibrk L, Ennishi D, Jessa S, Chong L, Thomas N, Pararajalingam P, Meissner B, Boyle M, Davidson J, Bushell KR, Lai D, Farinha P, Slack GW, Morin GB, Shah S, Sen D, Jones SJM, Mungall AJ, Gascoyne RD, Audas TE, Unrau P, Marra MA, Connors JM, Steidl C, Scott DW, Morin RD. Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma. Nat Commun. 2018 Oct 1;9(1):4001. PMCID: PMC6167379

Morin RD, Assouline S, Alcaide M, Mohajeri A, Johnston RL, Chong L, Grewal J, Yu S, Fornika D, Bushell K, Nielsen TH, Petrogiannis-Haliotis T, Crump M, Tosikyan A, Grande BM, MacDonald D, Rousseau C, Bayat M, Sesques P, Froment R, Albuquerque M, Monczak Y, Oros KK, Greenwood C, Riazalhosseini Y, Arseneault M, Camlioglu E, Constantin A, Pan-Hammarstrom Q, Peng R, Mann KK, Johnson NA. Genetic Landscapes of Relapsed and Refractory Diffuse Large B-Cell Lymphomas. Clin Cancer Res. 2016 May 1;22(9):2290–2300.