Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma.

摘要: Primary mediastinal B-cell lymphoma (PMBL) is a separate entity of aggressive lymphoma, characterized by constitutive activation janus kinase-signal transducer and activator transcription (JAK-STAT) signaling pathway, also observed in Hodgkin lymphoma. Although many cancers exhibit JAK-STAT pathway activation, mutations STAT genes have not been reported neoplasms. Here, we show that MedB-1 PMBL-derived L1236 Hodgkin-derived cell lines 20 55 (36%) PMBL cases harbor heterozygous missense STAT6 DNA binding domain, whereas no mutation was found 25 diffuse large samples. In 3 cases, somatic origin indicated the absence nontumoral tissue. The pattern different from classical features hypermutations. mutant proteins showed decreased ability transfected HEK cells, but decrease expression canonical target with mutated gene. oncogenic properties remain to be determined, their recurrent selection strongly argues for involvement pathogenesis this