Table of Contents

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

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a gain of function (GOF).1

Relevance tier by entity

Entity Tier Description
DLBCL 1 High-confidence DLBCL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 16 0.0147 [0.0075,0.0218]
DLBCL GAMBL with Reddy 2,088 31 0.0148 [0.0097,0.02]
DLBCL BC 231 6 0.0260 [0.0055,0.0465]
DLBCL Dana-Farber 303 2 0.0066 [0,0.0157]
DLBCL NCI 470 6 0.0128 [0.0026,0.0229]
DLBCL Reddy 999 15 0.0150 [0.0075,0.0226]
DLBCL DLBCL_ICGC 85 2 0.0235 [0,0.0558]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 3.4132 0 1.0000
FL 0.5337 0 1.0000
DLBCL 0.9222 0 0.2901

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

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Expression

History

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

References

1.
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
2.
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.

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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