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Cancer Cell DOI:10.1016/j.ccr.2012.07.014

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

Publication TypeJournal Article
Year of Publication2012
AuthorsMonti, S, Chapuy, B, Takeyama, K, Rodig, SJ, Hao, Y, Yeda, KT, Inguilizian, H, Mermel, C, Currie, T, Dogan, A, Kutok, JL, Beroukhim, R, Neuberg, D, Habermann, TM, Getz, G, Kung, AL, Golub, TR, Shipp, MA
JournalCancer Cell
Date Published2012 Sep 11
KeywordsCell Cycle, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p16, DNA Copy Number Variations, E2F Transcription Factors, Gene Expression Profiling, Genes, p16, Genes, p53, Humans, Ki-67 Antigen, Lymphoma, Large B-Cell, Diffuse, Molecular Sequence Data, Tumor Suppressor Protein p53

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.


Alternate JournalCancer Cell
PubMed ID22975378
PubMed Central IDPMC3778921
Grant ListP01 CA092625 / CA / NCI NIH HHS / United States
P01CA092625 / CA / NCI NIH HHS / United States