Integrative Analysis Reveals an Outcome-Associated and Targetable Pattern of p53 and Cell Cycle Deregulation in Diffuse Large B Cell Lymphoma Academic Article uri icon

Overview

MeSH Major

  • Cell Cycle
  • DNA Copy Number Variations
  • Genes, p53
  • Lymphoma, Large B-Cell, Diffuse
  • Tumor Suppressor Protein p53

abstract

  • Diffuse large B cell lymphoma (DLBCL) is a clinically and biologically heterogeneous disease with a high proliferation rate. By integrating copy number data with transcriptional profiles and performing pathway analysis in primary DLBCLs, we identified a comprehensive set of copy number alterations (CNAs) that decreased p53 activity and perturbed cell cycle regulation. Primary tumors either had multiple complementary alterations of p53 and cell cycle components or largely lacked these lesions. DLBCLs with p53 and cell cycle pathway CNAs had decreased abundance of p53 target transcripts and increased expression of E2F target genes and the Ki67 proliferation marker. CNAs of the CDKN2A-TP53-RB-E2F axis provide a structural basis for increased proliferation in DLBCL, predict outcome with current therapy, and suggest targeted treatment approaches.

publication date

  • September 11, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3778921

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2012.07.014

PubMed ID

  • 22975378

Additional Document Info

start page

  • 359

end page

  • 72

volume

  • 22

number

  • 3