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Nat Genet. 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.

Author information

1
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.
2
1] Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Bioinformatics Training Program, University of British Columbia, Vancouver, British Columbia, Canada.
3
Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
4
Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada.
5
Department of Pathology, University of Arizona, Tucson, Arizona, USA.
6
INSERM U955, Créteil, France.
7
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.
8
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.
9
1] Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada. [2] Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
10
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

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.

PMID:
24531327
DOI:
10.1038/ng.2900
[Indexed for MEDLINE]

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