Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature genetics, 2014-04, Vol.46 (4), p.329-335

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.