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

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.

DOI: 10.1016/j.ccr.2012.07.014
0100200300201220132014201520162017
Citations per Year

814 Citations

Semantic Scholar estimates that this publication has 814 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Monti2012IntegrativeAR, title={Integrative analysis reveals an outcome-associated and targetable pattern of p53 and cell cycle deregulation in diffuse large B cell lymphoma.}, author={Stefano Monti and Bjoern Chapuy and Kunihiko Takeyama and Scott J. Rodig and Yansheng Hao and Kelly T Yeda and Haig V. Inguilizian and Craig Mermel and Treeve Currie and Ahmet Dogan and Jeffery L. Kutok and Rameen Beroukhim and Donna S Neuberg and Thomas Matthew Habermann and Gad Getz and Andrew L Kung and Todd R. Golub and Margaret A. Shipp}, journal={Cancer cell}, year={2012}, volume={22 3}, pages={359-72} }