title: Identification of genes putatively involved in the pathogenesis of diffuse large B-cell lymphomas by integrative genomics.
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.
authors.affiliation: Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oudejans
authors.forename: Wessel N
authors.initials: WN
authors.lastname: van Wieringen
authors.forename: Serge J
authors.initials: SJ
authors.lastname: Smeets
authors.forename: Marianne
authors.initials: M
authors.lastname: Tijssen
authors.forename: Sjoerd J
authors.initials: SJ
authors.lastname: Vosse
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Mark A
authors.initials: MA
authors.lastname: van de Wiel
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
mesh_terms: D017209:Apoptosis; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D023281:Genomics / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D016133:Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results; D018709:Statistics, Nonparametric