Open AccessGerminal Center B Cell-Like (GCB) and Activated B Cell-Like (ABC) Type of Diffuse Large B Cell Lymphoma (DLBCL): Analysis of Molecular Predictors, Signatures, Cell Cycle State and Patient Survival
Author(s) -
Steffen Blenk,
Julia Cathérine Engelmann,
Markus Weniger,
Jörg Schultz,
Marcus Dittrich,
A. Rosenwald,
Hans Konrad MüllerHermelink,
Tobias Müller,
Thomas Dandekar
Publication year - 2007
Publication title -
cancer informatics.
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.606
H-Index - 31
ISSN - 1176-9351
DOI - 10.1177/117693510700300004
Subject(s) - bcl6 , germinal center , diffuse large b cell lymphoma , irf4 , gene , cancer research , b cell , oncology , biology , computational biology , lymphoma , medicine , genetics , transcription factor , antibody
Aiming to find key genes and events, we analyze a large data set on diffuse large B-cell lymphoma (DLBCL) gene-expression (248 patients, 12196 spots). Applying the loess normalization method on these raw data yields improved survival predictions, in particular for the clinical important group of patients with medium survival time. Furthermore, we identify a simplified prognosis predictor, which stratifies different risk groups similarly well as complex signatures. We identify specific, activated B cell-like (ABC) and germinal center B cell-like (GCB) distinguishing genes. These include early (e.g. CDKN3) and late (e.g. CDKN2C) cell cycle genes. Independently from previous classification by marker genes we confirm a clear binary class distinction between the ABC and GCB subgroups. An earlier suggested third entity is not supported. A key regulatory network, distinguishing marked over-expression in ABC from that in GCB, is built by: ASB13, BCL2, BCL6, BCL7A, CCND2, COL3A1, CTGF, FN1, FOXP1, IGHM, IRF4, LMO2, LRMP, MAPK10, MME, MYBL1, NEIL1 and SH3BP5. It predicts and supports the aggressive behaviour of the ABC subgroup. These results help to understand target interactions, improve subgroup diagnosis, risk prognosis as well as therapy in the ABC and GCB DLBCL subgroups.