title: Alterations of negative regulators of cytokine signalling in immunodeficiency-related non-Hodgkin lymphoma.
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.
authors.affiliation: Division of Hematology, 'Amedeo Avogadro' University of Eastern Piedmont, Novara, Italy. capello@med.unipmn.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Capello
authors.forename: Annunziata
authors.initials: A
authors.lastname: Gloghini
authors.forename: Gianluca
authors.initials: G
authors.lastname: Baldanzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Clara
authors.initials: C
authors.lastname: Deambrogi
authors.forename: Marco
authors.initials: M
authors.lastname: Lucioni
authors.forename: Daniela
authors.initials: D
authors.lastname: Piranda
authors.forename: Rosella
authors.initials: R
authors.lastname: Famà
authors.forename: Andrea
authors.initials: A
authors.lastname: Graziani
authors.forename: Michele
authors.initials: M
authors.lastname: Spina
authors.forename: Umberto
authors.initials: U
authors.lastname: Tirelli
authors.forename: Marco
authors.initials: M
authors.lastname: Paulli
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Fabiola
authors.initials: F
authors.lastname: Sinigaglia
mesh_terms: D045744:Cell Line, Tumor; D060965:Clonal Evolution; D016207:Cytokines / Q000502:physiology*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D016867:Immunocompromised Host; D053612:Janus Kinases / Q000502:physiology; D016483:Lymphoma, AIDS-Related / Q000235:genetics* / Q000503:physiopathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D016377:Organ Transplantation; D011183:Postoperative Complications / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics* / Q000502:physiology; D012189:Retrospective Studies; D050791:STAT Transcription Factors / Q000502:physiology; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D016207:Cytokines; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D050791:STAT Transcription Factors; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6