Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation

Oncogene. 2006 Apr 27;25(18):2679-84. doi: 10.1038/sj.onc.1209151.


The suppressors of cytokine signaling (SOCS) are critically involved in the regulation of cellular proliferation, survival, and apoptosis via cytokine-induced JAK/STAT signaling. SOCS-1 silencing by aberrant DNA methylation contributes to oncogenesis in various B-cell neoplasias and carcinomas. Recently, we showed an alternative loss of SOCS-1 function due to deleterious SOCS-1 mutations in a major subset of primary mediastinal B-cell lymphoma (PMBL) and in the PMBL line MedB-1, and a biallelic SOCS-1 deletion in PMBL line Karpas1106P. For both cell lines our previous data demonstrated retarded JAK2 degradation and sustained phospho-JAK2 action leading to enhanced DNA binding of phospho-STAT5. Here, we analysed SOCS-1 in laser-microdissected Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). We detected SOCS-1 mutations in HRS cells of eight of 19 cHL samples and in three of five Hodgkin lymphoma (HL)-derived cell lines by sequencing analysis. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells of cHL tumor tissue (P < 0.01). Collectively, these findings support the concept that PMBL and cHL share many overlapping features, and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Nucleus / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor*
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Lasers
  • Molecular Sequence Data
  • Mutation*
  • Phosphorylation
  • Reed-Sternberg Cells
  • Repressor Proteins / genetics*
  • STAT5 Transcription Factor / metabolism*
  • Sequence Homology, Amino Acid
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*


  • Intracellular Signaling Peptides and Proteins
  • Repressor Proteins
  • SOCS1 protein, human
  • STAT5 Transcription Factor
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins