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. 2014 Apr;46(4):329-35.
doi: 10.1038/ng.2900. Epub 2014 Feb 16.

Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma

Jay Gunawardana  1 , Fong Chun Chan  2 , Adèle Telenius  3 , Bruce Woolcock  3 , Robert Kridel  1 , King L Tan  3 , Susana Ben-Neriah  3 , Anja Mottok  3 , Raymond S Lim  3 , Merrill Boyle  3 , Sanja Rogic  4 , Lisa M Rimsza  5 , Chrystelle Guiter  6 , Karen Leroy  7 , Philippe Gaulard  7 , Corinne Haioun  8 , Marco A Marra  9 , Kerry J Savage  3 , Joseph M Connors  3 , Sohrab P Shah  10 , Randy D Gascoyne  1 , Christian Steidl  1
Affiliations

Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma

Jay Gunawardana et al. Nat Genet. 2014 Apr.

Abstract

Classical Hodgkin lymphoma and primary mediastinal B cell lymphoma (PMBCL) are related lymphomas sharing pathological, molecular and clinical characteristics. Here we discovered by whole-genome and whole-transcriptome sequencing recurrent somatic coding-sequence mutations in the PTPN1 gene. Mutations were found in 6 of 30 (20%) Hodgkin lymphoma cases, in 6 of 9 (67%) Hodgkin lymphoma-derived cell lines, in 17 of 77 (22%) PMBCL cases and in 1 of 3 (33%) PMBCL-derived cell lines, 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 Hodgkin lymphoma cell line KM-H2 resulted in hyperphosphorylation and overexpression of downstream oncogenic targets. Our data establish PTPN1 mutations as new drivers in lymphomagenesis.

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