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

Jay Gunawardana, Fong Chun Chan, Adèle Telenius, Bruce Woolcock, Robert Kridel, King L. Tan, Susana Ben-Neriah, Anja Mottok, Raymond S. Lim, Merrill Boyle, Sanja Rogic, Lisa M. Rimsza, Chrystelle Guiter, Karen Leroy, Philippe Gaulard, Corinne Haioun, Marco A. Marra, Kerry J. Savage, Joseph M. Connors, Sohrab P. ShahRandy D. Gascoyne, Christian Steidl

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105 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)329-335
Number of pages7
JournalNature Genetics
Volume46
Issue number4
DOIs
StatePublished - Apr 2014

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ASJC Scopus subject areas

  • Genetics

Cite this

Gunawardana, J., Chan, F. C., Telenius, A., Woolcock, B., Kridel, R., Tan, K. L., Ben-Neriah, S., Mottok, A., Lim, R. S., Boyle, M., Rogic, S., Rimsza, L. M., Guiter, C., Leroy, K., Gaulard, P., Haioun, C., Marra, M. A., Savage, K. J., Connors, J. M., ... Steidl, C. (2014). Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma. Nature Genetics, 46(4), 329-335. https://doi.org/10.1038/ng.2900