The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma

Andreas Rosenwald, George Wright, Adrian Wiestner, Wing C. Chan, Joseph M. Connors, Elias Campo, Randy D. Gascoyne, Thomas M. Grogan, H. Konrad Muller-Hermelink, Erlend B. Smeland, Michael Chiorazzi, Jena M. Giltnane, Elaine M. Hurt, Hong Zhao, Lauren Averett, Sarah Henrickson, Liming Yang, John Powell, Wyndham H. Wilson, Elaine S. JaffeRichard Simon, Richard D. Klausner, Emilio Montserrat, Francesc Bosch, Timothy C. Greiner, Dennis D. Weisenburger, Warren G. Sanger, Bhavana J. Dave, James C. Lynch, Julie Vose, James O. Armitage, Richard I. Fisher, Thomas P. Miller, Michael LeBlanc, German Ott, Stein Kvaloy, Harald Holte, Jan Delabie, Louis M. Staudt

Research output: Contribution to journalArticle

691 Scopus citations

Abstract

We used gene expression profiling to establish a molecular diagnosis of mantle cell lymphoma (MCL), to elucidate its pathogenesis, and to predict the length of survival of these patients. An MCL gene expression signature defined a large subset of MCLs that expressed cyclin D1 and a novel subset that lacked cyclin D1 expression. A precise measurement of tumor cell proliferation, provided by the expression of proliferation signature genes, identified patient subsets that differed by more than 5 years in median survival. Differences in cyclin D1 mRNA abundance synergized with INK4a/ARF locus deletions to dictate tumor proliferation rate and survival. We propose a quantitative model of the aberrant cell cycle regulation in MCL that provides a rationale for the design of cell cycle inhibitor therapy in this malignancy.

Original languageEnglish (US)
Pages (from-to)185-197
Number of pages13
JournalCancer Cell
Volume3
Issue number2
DOIs
StatePublished - Feb 2003

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Rosenwald, A., Wright, G., Wiestner, A., Chan, W. C., Connors, J. M., Campo, E., Gascoyne, R. D., Grogan, T. M., Muller-Hermelink, H. K., Smeland, E. B., Chiorazzi, M., Giltnane, J. M., Hurt, E. M., Zhao, H., Averett, L., Henrickson, S., Yang, L., Powell, J., Wilson, W. H., ... Staudt, L. M. (2003). The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell, 3(2), 185-197. https://doi.org/10.1016/S1535-6108(03)00028-X