Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation
Weniger, M.A.; Melzner, I.; Menz, C.K.; Wegener, S.; Bucur, A.J.; Dorsch, K.; Mattfeldt, T.; Barth, T.F.E.; Möller, P.
Verhandlungen der Deutschen Gesellschaft für Pathologie 90: 210-215
2006
ISSN/ISBN: 0070-4113 PMID: 17867599 Document Number: 595171
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. 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. 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). 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.