Table of Contents

Overview

Mutations in the DTX1 gene, which encodes the E3 ubiquitin ligase Deltex 1, have been identified in various B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). DTX1 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. There are numerous mutation hotspots in this gene with some leading to a truncated protein. DTX1 functions as a negative regulator of the Notch signaling pathway. Some DTX1 mutations impair its function, thereby dysregulating Notch signaling, which is crucial for normal B-cell development and function. Due to minimal support in the original primary data and very few mutations reported in subsequent BL studies, this gene is very unlikely to be relevant in BL.

Relevance tier by entity

Entity Tier Description
BL 3 Mutations are unlikely to be relevant to BL
DLBCL 1 High-confidence DLBCL gene
MZL 1 High-confidence MZL gene
PMBL 1 High-confidence PMBL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 122 0.1120 [0.0933,0.1308]
DLBCL GAMBL with Reddy 2,088 181 0.0867 [0.0746,0.0988]
DLBCL BC 231 16 0.0693 [0.0365,0.102]
DLBCL Dana-Farber 303 32 0.1056 [0.071,0.1402]
DLBCL NCI 470 64 0.1362 [0.1052,0.1672]
DLBCL Reddy 999 59 0.0591 [0.0444,0.0737]
DLBCL DLBCL_ICGC 85 10 0.1176 [0.0492,0.1861]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 31 0.0483 [0.0317,0.0649]
FL GAMBL with Crouch 1,189 74 0.0622 [0.0485,0.076]
FL BC 379 20 0.0528 [0.0303,0.0753]
FL Kalmbach 164 8 0.0488 [0.0158,0.0817]
FL Crouch 547 43 0.0786 [0.0561,0.1012]
FL FL_ICGC 99 3 0.0303 [0,0.0641]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 3.8612 9.3709 1.000
FL 1.9245 5.4025 0.124
DLBCL 0.9763 1.9056 0.019

aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chr12 113492311 113497546 TSS NA

DTX1 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr12 113496076 G>A V27M
chr12 113496081 G>A W28*
chr12 113496082 G>A E29K
chr12 113496083 A>G E29G
chr12 113496085 T>G W30G
chr12 113496087 G>A W30*
chr12 113496089 T>A L31Q
chr12 113496089 T>C L31P
chr12 113496096 G>C E33D
chr12 113496097 C>T H34Y
chr12 113496112 C>T P39S
chr12 113496115 T>C Y40H
chr12 113496116 A>C Y40S
chr12 113496116 A>G Y40C
chr12 113496117 C>G Y40*
chr12 113496121 G>C A42P
chr12 113496130 T>A C45S
chr12 113496132 C>A C45*
chr12 113496133 C>T H46Y
chr12 113496135 C>A H46Q
chr12 113496139 A>T I48F
chr12 113496140 T>A I48N
chr12 113496141 T>G I48M
chr12 113496148 G>A V51M
chr12 113496155 A>T K53M
chr12 113496156 G>C K53N
chr12 113496159 G>C E54D
chr12 113496162 CG>AA DA55ET
chr12 113496170 G>A G58D
chr12 113496173 C>A S59Y
chr12 113496173 C>T S59F
chr12 113496175 G>A V60M
chr12 113496191 T>C V65A
chr12 113496191 T>G V65G
chr12 113496196 G>A A67T
chr12 113496197 C>T A67V
chr12 113496201 G>C Q68H
chr12 113496202 C>T L69F
chr12 113496205 G>C V70L
chr12 113496208 C>G P71A
chr12 113496208 C>T P71S
chr12 113496210 CT>TC Y72H
chr12 113496212 A>G Y72C
chr12 113496213 C>A Y72*

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Expression

Representative Mutations

BL1

Rating ★ ☆ ☆ ☆ ☆

DLBCL2

Rating ★ ★ ★ ★ ☆

All Mutations

BL

1059 323 742

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2012-08-27 : Rossi : MZL 2012-12-01 : Love : BL 2013-01-01 : Zhang : DLBCL 2018-04-12 : Schmitz : DLBCL 2018-05-01 : Chapuy : DLBCL 2023-11-15 : Gomez : PMBL

References

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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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