Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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DUSP4 deficiency due to promoter hypermethylation drives oncogenic JNK signaling and tumor cell survival in diffuse large B-cell lymphoma (methylation profiling data)

ABSTRACT: The epigenetic dysregulation of tumor suppressor genes is a major driver of human carcinogenesis. We have combined genome-wide methylation analyses with functional screening to identify novel candidate tumor suppressor genes in diffuse large B-cell lymphoma (DLBCL). We find that the dual-specificity phosphatase DUSP4 is aberrantly silenced in nodal and extranodal DLBCL due to promoter hypermethylation; ectopic expression of wild type DUSP4, but not of a phosphatase-deficient mutant, dephosphorylates c-JUN N-terminal kinase (JNK) and induces apoptosis in DLBCL cells. JNK inhibition prevents DLBCL survival in vitro and in vivo, and synergizes strongly with inhibitors of chronic active B-cell receptor signaling. Our results provide a mechanistic basis for the clinical development of JNK inhibitors in DLBCL, alone or in synthetic lethal combinations. RNA-seq expression profiling data set related to this experiment was also deposited at ArrayExpress under accession number E-MTAB-2925: http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-2925/

ORGANISM(S): Homo sapiens

SUBMITTER: Mark Robinson

PROVIDER: E-MTAB-2926 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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DUSP4 deficiency due to promoter hypermethylation drives oncogenic JNK signaling and tumor cell survival in diffuse large B-cell lymphoma (methylation profiling data)

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