Ontology type: schema:ScholarlyArticle
2014-04
AUTHORSJay 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 Shah, Randy D Gascoyne, Christian Steidl
ABSTRACTClassical 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. More... »
PAGES329-335
http://scigraph.springernature.com/pub.10.1038/ng.2900
DOIhttp://dx.doi.org/10.1038/ng.2900
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/24531327
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