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 Jaffe, Richard 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, 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 Jaffe, Richard 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
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.
Source: PubMed