Submitted March 27, 2007
Accepted July 23, 2007
Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAK2 expression and activation of STAT6
Anja Mottok, Christoph Renne, Klaus Willenbrock, Martin-Leo Hansmann, and Andreas Brauninger*
Senckenberg Institute of Pathology, University of Frankfurt, Frankfurt, Germany
* Corresponding author; email: braeuninger{at}em.uni-frankfurt.de.
Aberrant activities of JAK/STAT signalling pathways have been observed in several hematological malignancies. Here we show high expression of JAK2 in the tumor cells of lymphocyte-predominant Hodgkin lymphoma in 85% of cases and activation of JAK2 in 39% of cases. STAT6, which is a target of JAK2, was activated in 50% of the cases. SOCS1 controls JAK2 activity and degradation. Mutations in SOCS1 of either somatic or germline origin were observed in micromanipulated tumor cells of 50% of cases. Most mutations truncated SOCS1 or caused replacement of amino acids in functional important regions. Activating mutations in exon 12 of JAK2, which are frequent in myeloproliferative diseases, were not observed. In lymphocyte-predominant Hodgkin lymphoma SOCS1 function may thus be frequently impaired by mutations and this may contribute to high JAK2 expression and activation of the JAK2/STAT6 pathway.
