Author/Authors :
Monti، نويسنده , , Stefano and Chapuy، نويسنده , , Bjoern and Takeyama، نويسنده , , Kunihiko and Rodig، نويسنده , , Scott J. and Hao، نويسنده , , Yansheng and Yeda، نويسنده , , Kelly T. and Inguilizian، نويسنده , , Haig and Mermel، نويسنده , , Craig and Currie، نويسنده , , Treeve and Dogan، نويسنده , , Ahmet and Kutok، نويسنده , , Jeffery L. and Beroukhim، نويسنده , , Rameen and Neuberg، نويسنده , , Donna and Habermann، نويسنده , , Thomas M. and Getz، نويسنده , , Gad and Kung، نويسنده , , Andrew L. and Golub، نويسنده , , Todd R. and Shipp، نويسنده , , Margaret A.، نويسنده ,
Abstract :
Summary
e 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.
