Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, Campo E, Gascoyne RD, Grogan TM, Muller-Hermelink HK, Smeland EB, Chiorazzi M, Giltnane JM, Hurt EM, Zhao H, Averett L, Henrickson S, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Montserrat E, Bosch F, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Fisher RI, Miller TP, LeBlanc M, Ott G, Kvaloy S, Holte H, Delabie J, Staudt LM
Cancer Cell. 2003 3 (2)
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.
MeSH Terms (26)ADP-Ribosylation Factors Adult Aged Aged, 80 and over Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p16 Cyclin D1 DNA-Binding Proteins Female Gene Expression Profiling Genes, Neoplasm Humans Lymphoma, Mantle-Cell Male Middle Aged Neoplasm Proteins Prognosis Protein-Serine-Threonine Kinases Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger RNA, Neoplasm Survival Rate Tumor Suppressor Protein p53 Tumor Suppressor Proteins Untranslated Regions