Open AccessMassive Transcriptional Perturbation in Subgroups of Diffuse Large B-Cell Lymphomas
Author(s) -
Maciej Rosołowski,
Jürgen Läuter,
D. S. Abramov,
Hans Drexler,
Michael Hummel,
Wolfram Klapper,
Roderick A.F. MacLeod,
Shoji Pellissery,
Friedemann Horn,
Reiner Siebert,
Markus Loeffler
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0076287
Subject(s) - gene , biology , phenotype , gene expression profiling , diffuse large b cell lymphoma , stromal cell , gene expression , cancer research , lymphoma , immune system , b cell , regulation of gene expression , genetics , microbiology and biotechnology , immunology , antibody
Based on the assumption that molecular mechanisms involved in cancerogenesis are characterized by groups of coordinately expressed genes, we developed and validated a novel method for analyzing transcriptional data called Correlated Gene Set Analysis (CGSA). Using 50 extracted gene sets we identified three different profiles of tumors in a cohort of 364 Diffuse large B-cell (DLBCL) and related mature aggressive B-cell lymphomas other than Burkitt lymphoma. The first profile had high level of expression of genes related to proliferation whereas the second profile exhibited a stromal and immune response phenotype. These two profiles were characterized by a large scale gene activation affecting genes which were recently shown to be epigenetically regulated, and which were enriched in oxidative phosphorylation, energy metabolism and nucleoside biosynthesis. The third and novel profile showed only low global gene activation similar to that found in normal B cells but not cell lines. Our study indicates novel levels of complexity of DLBCL with low or high large scale gene activation related to metabolism and biosynthesis and, within the group of highly activated DLBCLs, differential behavior leading to either a proliferative or a stromal and immune response phenotype.