DUSP2 - morinlab/LLMPP GitHub Wiki


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DUSP2

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)[@schuhmacherJUNBDUSP2SGK12019b; @hartmannHighlyRecurrentMutations2016b] 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.

History

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timeline
    title Publication timing
      2013-08-15 : Morin : DLBCL
      2021-07-15 : Duns : PMBL

Relevance tier by entity

Entity Tier Description
PMBL 1 high-confidence PMBL/cHL/GZL gene[@dunsCharacterizationDLBCLPMBL2021b]
DLBCL 1-a aSHM target and high-confidence DLBCL gene [@morinMutationalStructuralAnalysis2013]
FL 2-a aSHM target; Although recurrent, the relevance of mutations in FL is tenuous

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity source frequency (%)
DLBCL GAMBL genomes 10.13
DLBCL Schmitz cohort 12.55
DLBCL Reddy cohort 9.71
DLBCL Chapuy cohort 4.27
FL GAMBL genomes 2.31

Mutation pattern and selective pressure estimates

Entity aSHM Significant selection dN/dS (missense) dN/dS (nonsense)
BL Yes No 1.258 17.913
DLBCL Yes No 1.537 12.012
FL Yes No 3.206 0.000

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

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

DUSP2 Expression

References