Table of Contents

Overview

DUSP2 functions as a negative regulator of MAPK signaling, particularly affecting the ERK1/2 pathway. DUSP2 mutations have been reported in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T-cell/histiocyte-rich large B-cell lymphoma (T/HRLBCL)1,2 and they are relatively frequent in DLBCL.
DUSP2 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 ST2 genetic subgroup of DLBCL. This gene has some recurrent sites of mutations (hot spots). The mutation pattern in DLBCL implies the preferential accumulation of inactivating mutations.

Relevance tier by entity

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Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 103 0.0946 [0.0772,0.112]
DLBCL GAMBL with Reddy 2,088 200 0.0958 [0.0832,0.1084]
DLBCL BC 231 21 0.0909 [0.0538,0.128]
DLBCL Dana-Farber 303 13 0.0429 [0.0201,0.0657]
DLBCL NCI 470 59 0.1255 [0.0956,0.1555]
DLBCL Reddy 999 97 0.0971 [0.0787,0.1155]
DLBCL DLBCL_ICGC 85 10 0.1176 [0.0492,0.1861]
pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 13 0.0202 [0.0094,0.0311]
FL GAMBL with Crouch 1,189 13 0.0109 [0.005,0.0168]
FL BC 379 7 0.0185 [0.0049,0.032]
FL Kalmbach 164 3 0.0183 [0,0.0388]
FL Crouch 547 0 0.0002 [0,0.0013]
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 1.4723 16.4546 1
FL 3.0082 6.2264 1
DLBCL 0.8137 5.4445 0

aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chr2 96808901 96811913 intron-1 enhancer

DUSP2 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr2 96810877 C>G D73H
chr2 96810865 G>A R77W
chr2 96810842 C>G E84D
chr2 96810841 G>C L85V
chr2 96810730 G>A P122S
chr2 96810717 T>C Y126C
chr2 96810706 C>T G130R
chr2 96810597 C>T C138Y
chr2 96810582 C>T C143Y
chr2 96810574 C>T A146T

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Expression

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References

1.
Schuhmacher B, Bein J, Rausch T, Benes V, Tousseyn T, Vornanen M, Ponzoni M, Thurner L, Gascoyne R, Steidl C, Küppers R, Hansmann ML, Hartmann S. JUNB, DUSP2, SGK1, SOCS1 and CREBBP are frequently mutated in T-cell/histiocyte-rich large B-cell lymphoma. Haematologica. 2019 Feb;104(2):330–337. PMCID: PMC6355500
2.
Hartmann S, Schuhmacher B, Rausch T, Fuller L, Döring C, Weniger M, Lollies A, Weiser C, Thurner L, Rengstl B, Brunnberg U, Vornanen M, Pfreundschuh M, Benes V, Küppers R, Newrzela S, Hansmann M-L. Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma. Leukemia. 2016 Apr;30(4):844–853.
3.
Duns G, Viganò E, Ennishi D, Sarkozy C, Hung SS, Chavez E, Takata K, Rushton C, Jiang A, Ben-Neriah S, Woolcock BW, Slack GW, Hsi ED, Craig JW, Hilton LK, Shah SP, Farinha P, Mottok A, Gascoyne RD, Morin RD, Savage KJ, Scott DW, Steidl C. Characterization of DLBCL with a PMBL gene expression signature. Blood. 2021 Jul 15;138(2):136–148.
4.
Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL, Novak AJ, Dogan A, Ansell SM, Link BK, Zou L, Gould J, Saksena G, Stransky N, Rangel-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Hernández-Lemus E, Schwarz-Cruz y Celis A, Imaz-Rosshandler I, Ojesina AI, Jung J, Pedamallu CS, Lander ES, Habermann TM, Cerhan JR, Shipp MA, Getz G, Golub TR. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3879–3884. PMCID: PMC3309757
5.
Morin RD, Mungall K, Pleasance E, Mungall AJ, Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, Corbett RD, Chan FC, Mendez-Lago M, Trinh DL, Bolger-Munro M, Taylor G, Hadj Khodabakhshi A, Ben-Neriah S, Pon J, Meissner B, Woolcock B, Farnoud N, Rogic S, Lim EL, Johnson NA, Shah S, Jones S, Steidl C, Holt R, Birol I, Moore R, Connors JM, Gascoyne RD, Marra MA. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood. 2013 Aug 15;122(7):1256–1265. PMCID: PMC3744992

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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