Integrative analysis reveals an outcome-associated and targetable pattern of p53 and cell cycle deregulation in diffuse large B cell lymphoma.

Cancer Cell
Authors
Keywords
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.

Year of Publication
2012
Journal
Cancer Cell
Volume
22
Issue
3
Pages
359-72
Date Published
2012 Sep 11
ISSN
1878-3686
URL
DOI
10.1016/j.ccr.2012.07.014
PubMed ID
22975378
PubMed Central ID
PMC3778921
Links
Grant list
P01 CA092625 / CA / NCI NIH HHS / United States
P01CA092625 / CA / NCI NIH HHS / United States