Hematol Oncol. 2012 Apr 9. doi: 10.1002/hon.2010.

Alterations of negative regulators of cytokine signalling in immunodeficiency-related non-Hodgkin lymphoma.

Capello D, Gloghini A, Baldanzi G, Martini M, Deambrogi C, Lucioni M, Piranda D, Famą R, Graziani A, Spina M, Tirelli U, Paulli M, Larocca LM, Gaidano G, Carbone A, Sinigaglia F.
SourceDivision of Hematology, 'Amedeo Avogadro' University of Eastern Piedmont, Novara, Italy; Laboratory of Clinical Biochemistry and Molecular Biology, 'Amedeo Avogadro' University of Eastern Piedmont, Novara, Italy. capello@med.unipmn.it.

Abstract
We investigated immunodeficiency-related non-Hodgkin lymphoma for the presence of molecular alterations affecting negative regulators of the Janus family protein tyrosine kinase/signal transducer and activator of transcription pathway. Protein tyrosine phosphatase, non-receptor type 6/Src homology 2-containing tyrosine phosphatase-1 epigenetic silencing was recurrent in primary effusion lymphoma (100%), and diffuse large B-cell lymphoma (63%), with a higher prevalence in the non-germinal centre subtype, and was associated with the activation of the Janus family protein tyrosine kinase/signal transducer and activator of transcription 3 pathway. Suppressor of cytokine signalling (SOCS)1 and SOCS3 epigenetic silencing were occasionally detected, whereas SOCS1 was frequently mutated in diffuse large B-cell lymphoma and polymorphic post-transplant lymphoproliferative disorders, possibly as a cause of aberrant somatic hypermutation. However, the mutation profile of the coding region of the gene was different from that expected from the aberrant somatic hypermutation process, suggesting that, at least in some cases, SOCS1 mutations may have been selected for their functional activity. Copyright © 2012 John Wiley & Sons, Ltd.
 

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