Novel Submicroscopic Genomic Alterations Identified in Diffuse Large B-Cell Lymphoma Using High-Resolution Oligonucleotide-Based Array CGH Analysis
JL Christal, RA Higgins, AR Bolla, RS Robetorye. The University of Texas Health Science Center at San Antonio, San Antonio, TX
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and is comprised of clinically heterogeneous groups. This heterogeneity has led to attempts to identify distinct subgroups of DLBCL using immunophenotypic methods, gene expression profiles, and molecular cytogenetic alterations. Here, we report analysis of a total of 85 cases of DLBCLs and DLBCL cell lines using high-resolution oligonucleotide-based array comparative genomic hybridization (array CGH) in order to identify novel recurrent submicroscopic genomic imbalances in DLBCL. These alterations may help to identify genes that have potential clinical and biological signficance.
Design: Fifty-seven nodal and extranodal DLBCLs and 28 DLBCL cell lines were analyzed using Agilent Human Genome 44K CGH oligonucleotide arrays (Agilent Technologies, Santa Clara, CA) according to the manufacturer's recommendations. Slides were scanned with an Agilent Scanner, and the data were analyzed with Agilent Feature Extraction and CGH Analytics software. Array CGH results for each case were also subjected to penetrance analysis to identify common regions of genomic alteration.
Results: Array CGH analysis and penetrance plots identified several previously described genomic regions with frequent copy number alterations in DLBCL, including 1q gain, 2p gain (includes REL), 6q loss, 8q gain (includes MYC), 9p21 loss (includes CDKN2A and CDKN2B; Figure 1), and 17p loss (includes TP53). However, additional regions exhibited novel recurrent submicroscopic genomic alterations, including gains at 7p22 and 7q22, and losses at 1p36, 2p12, 14q32, 19p13, 19q13, and 22q11.
Conclusions: High-resolution oligonucleotide-based array CGH identified many previously described genomic alterations associated with DLBCL. In addition, several novel submicroscopic genomic alterations of potential importance were identified in these lymphomas. Additional studies will be required to identify relevant genes in these newly identified regions to determine whether alterations in the expression of these genes might play a role in the pathogenesis of DLBCL.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 221, Tuesday Morning