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bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true

DDX3X

Overview

Mutations in the DDX3X gene, which encodes an RNA helicase involved in various aspects of RNA metabolism, have significant implications in B-cell lymphomas, including BL, DLBCL, and other related malignancies and are particularly enriched within MYC-translocated tumors and those expressing the dark zone signature (DZsig).[@ennishiDoubleHitGeneExpression2019] These mutations are predominantly loss-of-function (LOF) mutations, affecting the helicase domain of the protein. Missense mutations are predominantly found in male patients and rarely in females, hence showing a sex-specific pattern.[@gongSequentialInverseDysregulation2021]

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%%
timeline
    title Publication timing
2012-10-04 : Schmitz : BL 
2017-10-10 : Reddy : DLBCL
2018-04-12 : Schmitz : DLBCL
2018-10-01 : Arthur : DLBCL
2019-09-05 : Mottok : PMBL

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene[@mottokIntegrativeGenomicAnalysis2019b]
	1	high-confidence BL gene [@schmitzBurkittLymphomaPathogenesis2012]
	1	high-confidence DLBCL gene [@reddyGeneticFunctionalDrivers2017; @schmitzGeneticsPathogenesisDiffuse2018a; @arthurGenomewideDiscoverySomatic2018]
	2	Although recurrent, the relevance of mutations in FL is tenuous

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	44.34
BL	Thomas cohort	48.70
BL	Panea cohort	39.60
DLBCL	GAMBL genomes	8.80
DLBCL	Schmitz cohort	4.68
DLBCL	Reddy cohort	4.50
DLBCL	Chapuy cohort	5.56
FL	GAMBL genomes	2.54

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	Yes	19.270	125.826
DLBCL	Yes	No	3.193	8.744
FL	Yes	No	11.136	21.489

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chrX	42800580	42804184	intergenic	NA

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

DDX3X Expression

References