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

Oncogene volume 25, pages 2679–2684 (2006)Cite this article

Abstract

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.

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Acknowledgements

We thank Michaela Buck for excellent technical assistance. This work was supported by a grant of the Deutsche Krebshilfe, Mildred Scheel Stiftung (Grant number 106367) to TFE Barth and P Möller.

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  1. M A Weniger and I Melzner: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, University of Ulm, Ulm, Germany

    M A Weniger, I Melzner, C K Menz, S Wegener, A J Bucur, K Dorsch, T Mattfeldt, T F E Barth & P Möller

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  1. M A Weniger
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Correspondence to P Möller.

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Weniger, M., Melzner, I., Menz, C. et al. Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation. Oncogene 25, 2679–2684 (2006). https://doi.org/10.1038/sj.onc.1209151

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