Oncogenically active MYD88 mutations in human lymphoma

Vu N. Ngo, Ryan M. Young, Roland Schmitz, Sameer Jhavar, Wenming Xiao, Kian-Huat Lim, Holger Kohlhammer, Weihong Xu, Yandan Yang, Hong Zhao, Arthur L. Shaffer, Paul Romesser, George Wright, John Powell, Andreas Rosenwald, Hans Konrad Muller-Hermelink, German Ott, Randy D. Gascoyne, Joseph M. Connors, Lisa M. Rimsza, Elias Campo, Elaine S. Jaffe, Jan Delabie, Erlend B. Smeland, Richard I. Fisher, Rita M. Braziel, Raymond R. Tubbs, J. R. Cook, Denny D. Weisenburger, Wing C. Chan and Louis M. Staudt ()
Additional contact information
Vu N. Ngo: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Ryan M. Young: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Roland Schmitz: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Sameer Jhavar: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Wenming Xiao: Bioinformatics and Molecular Analysis Section, Center for Information Technology, National Institutes of Health
Kian-Huat Lim: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Holger Kohlhammer: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Weihong Xu: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Yandan Yang: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Hong Zhao: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Arthur L. Shaffer: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Paul Romesser: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
George Wright: Biometric Research Branch, DCTD, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
John Powell: Bioinformatics and Molecular Analysis Section, Center for Information Technology, National Institutes of Health
Andreas Rosenwald: University of Würzburg, 97080 Würzburg, Germany
Hans Konrad Muller-Hermelink: University of Würzburg, 97080 Würzburg, Germany
German Ott: Robert-Bosch-Krankenhaus, and Dr Margarete Fischer-Bosch Institute for Clinical Pharmacology, 70376 Stuttgart, Germany
Randy D. Gascoyne: British Columbia Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada
Joseph M. Connors: British Columbia Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada
Lisa M. Rimsza: University of Arizona
Elias Campo: Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
Elaine S. Jaffe: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Jan Delabie: Pathology Clinic, Rikshospitalet University Hospital, N-0310 Oslo, Norway
Erlend B. Smeland: Institute for Cancer Research, Rikshospitalet University Hospital and Center for Cancer Biomedicine, University of Oslo, N-0310 Oslo, Norway
Richard I. Fisher: Southwest Oncology Group, 24 Frank Lloyd Wright Drive
Rita M. Braziel: Southwest Oncology Group, 24 Frank Lloyd Wright Drive
Raymond R. Tubbs: Southwest Oncology Group, 24 Frank Lloyd Wright Drive
J. R. Cook: Southwest Oncology Group, 24 Frank Lloyd Wright Drive
Denny D. Weisenburger: University of Nebraska Medical Center
Wing C. Chan: University of Nebraska Medical Center
Louis M. Staudt: Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA

Nature, 2011, vol. 470, issue 7332, 115-119

Abstract: MYD88 signalling in cancer RNA interference screening and high-throughput RNA resequencing have been used to reveal oncogenic mutations in the signalling adapter MYD88 in human lymphomas. One amino acid substitution, L265P, was found in 29% of biopsies from patients with the activated B-cell-like subtype of diffuse large B-cell lymphoma. The same mutation was observed with lower frequency in mucosa-associated lymphoid tissue lymphomas. MYD88 mediates signalling by Toll-like receptors, and the mutations, most of which affect the same amino acid, were shown to activate the pathway and promote cancer cell survival.

Date: 2011
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DOI: 10.1038/nature09671

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