title: [Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation].
abstract: OBJECTIVE
  Suppressors of cytokine signaling (SOCS) negatively regulate Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling involved in proliferation, survival, and apoptosis. We previously showed a loss of SOCS-1 function due to deleterious mutations in a major subset of mediastinal B-cell lymphoma (MBL). In MBL cell lines this leads to retarded JAK2 degradation and sustained phospho-STAT5 action results in enhanced DNA binding of phospho-STAT5.
  
  
  METHODS
  To investigate the SOCS-1 gene we laser-microdissected Hodgkin-and Reed-Sternberg (HRS) cells of 19 classical Hodgkin lymphoma (cHL) and performed sequencing analysis. To assess phospho-STAT5 status immunohistochemistry on the corresponding paraffin-embedded cHL tumor tissue was done.
  
  
  RESULTS
  We detected mutations of the SOCS-1 gene in HRS cells of 8 of 19 cHL samples and in 3 of 5 cHL-derived cell lines. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells (P <0.01).
  
  
  CONCLUSIONS
  In conclusion, these findings support the concept that MBL and cHL share overlapping features and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas.
authors.affiliation: Abteilung Pathologie, Universität Ulm.
authors.forename: M A
authors.initials: MA
authors.lastname: Weniger
authors.forename: I
authors.initials: I
authors.lastname: Melzner
authors.forename: C K
authors.initials: CK
authors.lastname: Menz
authors.forename: S
authors.initials: S
authors.lastname: Wegener
authors.forename: A J
authors.initials: AJ
authors.lastname: Bucur
authors.forename: K
authors.initials: K
authors.lastname: Dorsch
authors.forename: T
authors.initials: T
authors.lastname: Mattfeldt
authors.forename: T F E
authors.initials: TF
authors.lastname: Barth
authors.forename: P
authors.initials: P
authors.lastname: Möller
mesh_terms: D002467:Cell Nucleus / Q000473:pathology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010766:Phosphorylation; D016539:Reed-Sternberg Cells / Q000473:pathology; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: C108944:SOCS1 protein, human; D050799:STAT5 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins