Table of Contents

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).1 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.2

Experimental Evidence

Driver mutations affecting this gene in DLBCL/BL have been experimentally demonstrated to cause a reduction or loss of function (LOF).2

Relevance tier by entity

Cannot include /table1_DDX3X - does not exist yet

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 59 0.0542 [0.0407,0.0676]
DLBCL GAMBL with Reddy 2,088 104 0.0498 [0.0405,0.0591]
DLBCL BC 231 17 0.0736 [0.0399,0.1073]
DLBCL Dana-Farber 303 15 0.0495 [0.0251,0.0739]
DLBCL NCI 470 22 0.0468 [0.0277,0.0659]
DLBCL Reddy 999 45 0.0450 [0.0322,0.0579]
DLBCL DLBCL_ICGC 85 5 0.0588 [0.0088,0.1088]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 15 0.0234 [0.0117,0.035]
FL GAMBL with Crouch 1,189 26 0.0219 [0.0136,0.0302]
FL BC 379 8 0.0211 [0.0066,0.0356]
FL Kalmbach 164 4 0.0244 [8e-04,0.048]
FL Crouch 547 11 0.0201 [0.0083,0.0319]
FL FL_ICGC 99 3 0.0303 [0,0.0641]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 136 0.4391 [0.3839,0.4942]
BL GAMBL without ICGC/Zhou 320 142 0.4432 [0.3888,0.4975]
BL GAMBL with Panea 410 176 0.4283 [0.3806,0.476]
BL BLGSP 219 102 0.4658 [0.3997,0.5318]
BL Zhou/ICGC 90 34 0.3778 [0.2776,0.4779]
BL Panea 101 40 0.3960 [0.3007,0.4914]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 17.6767 123.7546 0e+00
FL 5.7751 4.7395 1e+00
DLBCL 2.1162 4.1623 6e-04

aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chrX 42800580 42804184 intergenic NA

Cannot include /browser_DDX3X.md - does not exist yet

Expression

Cannot include /mermaid_DDX3X.md - does not exist yet

References

1.
Ennishi D, Jiang A, Boyle M, Collinge B, Grande BM, Ben-Neriah S, Rushton C, Tang J, Thomas N, Slack GW, Farinha P, Takata K, Miyata-Takata T, Craig J, Mottok A, Meissner B, Saberi S, Bashashati A, Villa D, Savage KJ, Sehn LH, Kridel R, Mungall AJ, Marra MA, Shah SP, Steidl C, Connors JM, Gascoyne RD, Morin RD, Scott DW. Double-Hit Gene Expression Signature Defines a Distinct Subgroup of Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2019 Jan 20;37(3):190–201. PMCID: PMC6804880
2.
Gong C, Krupka JA, Gao J, Grigoropoulos NF, Giotopoulos G, Asby R, Screen M, Usheva Z, Cucco F, Barrans S, Painter D, Zaini NBM, Haupl B, Bornelöv S, Ruiz De Los Mozos I, Meng W, Zhou P, Blain AE, Forde S, Matthews J, Khim Tan MG, Burke GAA, Sze SK, Beer P, Burton C, Campbell P, Rand V, Turner SD, Ule J, Roman E, Tooze R, Oellerich T, Huntly BJ, Turner M, Du MQ, Samarajiwa SA, Hodson DJ. Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis. Molecular Cell. 2021;
3.
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
4.
Mottok A, Hung SS, Chavez EA, Woolcock B, Telenius A, Chong LC, Meissner B, Nakamura H, Rushton C, Viganò E, Sarkozy C, Gascoyne RD, Connors JM, Ben-Neriah S, Mungall A, Marra MA, Siebert R, Scott DW, Savage KJ, Steidl C. Integrative genomic analysis identifies key pathogenic mechanisms in primary mediastinal large B-cell lymphoma. Blood. 2019 Sep 5;134(10):802–813.
5.
Reddy A, Zhang J, Davis NS, Moffitt AB, Love CL, Waldrop A, Leppa S, Pasanen A, Meriranta L, Karjalainen-Lindsberg ML, Nørgaard P, Pedersen M, Gang AO, Høgdall E, Heavican TB, Lone W, Iqbal J, Qin Q, Li G, Kim SY, Healy J, Richards KL, Fedoriw Y, Bernal-Mizrachi L, Koff JL, Staton AD, Flowers CR, Paltiel O, Goldschmidt N, Calaminici M, Clear A, Gribben J, Nguyen E, Czader MB, Ondrejka SL, Collie A, Hsi ED, Tse E, Au-Yeung RKH, Kwong YL, Srivastava G, Choi WWL, Evens AM, Pilichowska M, Sengar M, Reddy N, Li S, Chadburn A, Gordon LI, Jaffe ES, Levy S, Rempel R, Tzeng T, Happ LE, Dave T, Rajagopalan D, Datta J, Dunson DB, Dave SS. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. Cell. 2017 Oct;171(2):481–494.e15. PMCID: PMC5659841
6.
Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, Wright G, Shaffer AL, Hodson DJ, Buras E, Liu X, Powell J, Yang Y, Xu W, Zhao H, Kohlhammer H, Rosenwald A, Kluin P, Müller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Ogwang MD, Reynolds SJ, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pittaluga S, Wilson W, Waldmann TA, Rowe M, Mbulaiteye SM, Rickinson AB, Staudt LM. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012 Oct 4;490(7418):116–120. PMCID: PMC3609867
7.
Schmitz R, Wright GW, Huang DW, Johnson CA, Phelan JD, Wang JQ, Roulland S, Kasbekar M, Young RM, Shaffer AL, Hodson DJ, Xiao W, Yu X, Yang Y, Zhao H, Xu W, Liu X, Zhou B, Du W, Chan WC, Jaffe ES, Gascoyne RD, Connors JM, Campo E, Lopez-Guillermo A, Rosenwald A, Ott G, Delabie J, Rimsza LM, Tay Kuang Wei K, Zelenetz AD, Leonard JP, Bartlett NL, Tran B, Shetty J, Zhao Y, Soppet DR, Pittaluga S, Wilson WH, Staudt LM. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. N Engl J Med. 2018 Apr 12;378(15):1396–1407. PMCID: PMC6010183

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.

Disclaimer

The content in these pages has been populated, in part, by an automated process. Although we have scrutinized every page to ensure accuracy, errors will inevitably exist. If you find an error please report it as an issue and we will address it.

License

This work is licensed under a Creative Commons Attribution 4.0 International License.

You are free to:

Share — copy and redistribute the material in any medium or format for any purpose, even commercially.

Adapt — remix, transform, and build upon the material for any purpose, even commercially. The licensor cannot revoke these freedoms as long as you follow the license terms.