Recurrent Somatic Mutations of PTPN1 in Primary Mediastinal B cell lymphoma and Hodgkin Lymphoma

Hodgkin lymphoma (HL) and primary mediastinal B cell lymphoma (PMBCL) are related lymphomas sharing pathological, molecular and clinical characteristics. Here, we discovered recurrent somatic coding sequence mutations of the tyrosine phosphatase gene PTPN1 in the tumor genomes and transcriptomes of these B cell lymphomas (6 of 30 or in 20% of HL cases and 13 of 49 or in 27% of PMBCL cases), consisting of nonsense, missense and frameshift mutations. We demonstrate that PTPN1 mutations lead to reduced phosphatase activity and increased phosphorylation of JAK-STAT pathway members. Moreover, silencing of PTPN1 by RNA interference in HL cell line KM-H2 resulted in hyperphosphorylation and overexpression of downstream oncogenic targets. Our data establish PTPN1 mutations as novel drivers in B cell lymphomagenesis.EGA study EGAS00001000554