Mutation and genomic deletion status of ataxia telangiectasia mutated (ATM) and p53 confer specific gene expression profiles in mantle cell lymphoma

Timothy C. Greiner, Chiranjib Dasgupta, Vincent V. Ho, Dennis D. Weisenburger, Lynette M. Smith, James C. Lynch, Julie M. Vose, Kai Fu, James O. Armitage, Rita M. Braziel, Elias Campo, Jan Delabie, Randy D. Gascoyne, Elaine S. Jaffe, Hans K. Muller-Hermelink, German Ott, Andreas Rosenwald, Louis M. Staudt, Michael Y. Im, Mazen W. KaramanBrian L. Pike, Wing C. Chan, Joseph G. Hacia

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Although mantle cell lymphoma (MCL) frequently harbors inactivated a ataxia telangiectasia mutated (ATM) and p53 alleles, little is known about the molecular phenotypes caused by these genetic changes. We identified point mutations and genomic deletions in these genes in a series of cyclin D1-positive MCL cases and correlated genotype with gene expression profiles and overall survival. Mutated and/or deleted ATM and p53 alleles were found in 56% (40/72) and 26% (21/82) of the cases examined, respectively. Although MCL patients with inactive p53 alleles showed a significant reduction in median overall survival, aberrant ATM status did not predict for survival. Nevertheless, specific gene expression signatures indicative of the mutation and genomic deletion status of each gene were identified that were different from wild-type cases. These signatures were comprised of a select group of genes related to apoptosis, stress responses, and cell cycle regulation that are relevant to ATM or p53 function. Importantly, we found the molecular signatures are different between cases with mutations and deletions, because the latter are characterized by loss of genes colocalized in the same chromosome region of ATM or p53. This information on molecular phenotypes may provide new areas of investigation for ATM function or may be exploited by designing specific therapies for MCL cases with p53 aberrations.

Original languageEnglish (US)
Pages (from-to)2352-2357
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number7
DOIs
StatePublished - Feb 14 2006

Keywords

  • Cancer
  • Cell cycle
  • Genetics
  • Microarray
  • Signature

ASJC Scopus subject areas

  • General

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