Integrative Analysis Reveals an Outcome-associated and Targetable Pattern of P53 and Cell Cycle Deregulation in Diffuse Large B Cell Lymphoma

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2012 Sep 15

PMID 22975378

Citations 114

Authors

Stefano Monti

Bjoern Chapuy

Kunihiko Takeyama

Scott J Rodig

Yansheng Hao

Kelly T Yeda

Haig Inguilizian

Craig Mermel

Treeve Currie

Ahmet Dogan

Jeffery L Kutok

Rameen Beroukhim

Donna Neuberg

Thomas M Habermann

Gad Getz

Andrew L Kung

Todd R Golub

Margaret A Shipp

Affiliations

Soon will be listed here.

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.

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