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

Cancer Cell. 2003 Feb;3(2):185-97. doi: 10.1016/s1535-6108(03)00028-x.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Cyclin D1 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • DNA-Binding Proteins
  • Female
  • Gene Expression Profiling
  • Genes, Neoplasm / genetics*
  • Humans
  • Lymphoma, Mantle-Cell / genetics*
  • Lymphoma, Mantle-Cell / mortality*
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins
  • Untranslated Regions / genetics

Substances

  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Untranslated Regions
  • Cyclin D1
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases
  • ADP-Ribosylation Factors