Identification of genes putatively involved in the pathogenesis of diffuse large B-cell lymphomas by integrative genomics

✍ Scribed by Joost J. Oudejans; Wessel N. van Wieringen; Serge J. Smeets; Marianne Tijssen; Sjoerd J. Vosse; Chris J. L. M. Meijer; Gerrit A. Meijer; Mark A. van de Wiel; Bauke Ylstra

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 235 KB
• Volume: 48
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.20632

✦ Synopsis

Abstract

Diffuse large B‐cell lymphomas (DLBCL) are highly heterogeneous with regard to clinical presentation and outcome. DLBCL copy number aberrations have been identified previously, of which the deletion at 6q21‐24 was significantly associated with a highly favorable clinical response to chemotherapy. In this study, we aimed to identify genes implicated in this and other genomic regions with recurrent losses and/or gains. To identify implicated genes, we superimposed array comparative genomic hybridization (aCGH) data onto a microarray expression dataset of 42 clinically well‐characterized primary nodal DLBCL biopsies. We confirmed that loss of 6q21‐24 is significantly associated with a highly favorable clinical response to chemotherapy. Our approach identified 316 significant genes restricted to 32 chromosomal regions, including 24 genes identified at 6q21‐24. In an independent dataset, 18% of overexpressed genes in gained regions and 55% of down‐regulated genes in deleted regions were validated. In summary, using integrative genomics novel onco and tumor suppressor genes were identified in DLBCL that were not recognized by expression profiling alone. © 2008 Wiley‐Liss, Inc.