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Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma.
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.
Afiliação
  • Gunawardana J; 1] Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
  • Chan FC; 1] Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Bioinformatics Training Program, University of British Columbia, Vancouver, British Columbia, Canada.
  • Telenius A; Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Woolcock B; Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Kridel R; 1] Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
  • Tan KL; Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Ben-Neriah S; Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Mottok A; Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Lim RS; Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Boyle M; Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Rogic S; Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada.
  • Rimsza LM; Department of Pathology, University of Arizona, Tucson, Arizona, USA.
  • Guiter C; INSERM U955, Créteil, France.
  • Leroy K; 1] INSERM U955, Créteil, France. [2] Université Paris Est, Créteil, France. [3] Département de Pathologie-Service d'Hématologie-Plateforme de Ressources Biologiques, Groupe Hospitalier Henri-MONDOR, Assistance Publique-Hôpitaux de Paris, Créteil, France.
  • Gaulard P; 1] INSERM U955, Créteil, France. [2] Université Paris Est, Créteil, France. [3] Département de Pathologie-Service d'Hématologie-Plateforme de Ressources Biologiques, Groupe Hospitalier Henri-MONDOR, Assistance Publique-Hôpitaux de Paris, Créteil, France.
  • Haioun C; 1] Université Paris Est, Créteil, France. [2] Département de Pathologie-Service d'Hématologie-Plateforme de Ressources Biologiques, Groupe Hospitalier Henri-MONDOR, Assistance Publique-Hôpitaux de Paris, Créteil, France.
  • Marra MA; 1] Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
  • Savage KJ; Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Connors JM; Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • Shah SP; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
  • Gascoyne RD; 1] Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
  • Steidl C; 1] Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Nat Genet ; 46(4): 329-35, 2014 Apr.
Article em En | MEDLINE | ID: mdl-24531327
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Hodgkin / Linfoma de Células B / Proteína Tirosina Fosfatase não Receptora Tipo 1 / Neoplasias do Mediastino / Mutação Limite: Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Hodgkin / Linfoma de Células B / Proteína Tirosina Fosfatase não Receptora Tipo 1 / Neoplasias do Mediastino / Mutação Limite: Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article