Array comparative genomic hybridization reveals genomic copy number changes associated with outcome in diffuse large B-cell lymphomas
- 15 March 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 107 (6), 2477-2485
- https://doi.org/10.1182/blood-2005-07-2950
Abstract
To identify, in high-resolution regions of DNA, the copy number changes associated with outcome in patients with diffuse large B-cell lymphoma (DLBCL), a disease with an approximately 50% mortality rate, we performed array comparative genomic hybridization (array-CGH) on specimens from 64 patients with newly diagnosed DLBCL treated with anthracycline-based chemotherapy. For the entire cohort, 55 commonly gained/lost regions, ranging in size from less than 1 Mbp to entire chromosomes, were identified using 1- to 2-Mbp and 2- to 4-Mbp resolution BAC arrays. Copy number changes of 9 minimal regions significantly correlated with overall survival, of which 6 were 10 Mbp or smaller. On multivariate analysis, loss of chromosomes 2 (2.4-4.1 Mbp) and 16 (33.8-35.6 Mbp) were found to be prognostic indicators of poor survival, independent of clinical features routinely used to predict outcome. Loss of chromosome 1 (78.2-79.1 Mbp) was predictive of good outcome. For a subset of 55 specimens classified according to cell-of-origin expression signature subtype, gain of chromosome 12 (45.4-53.8 Mbp) was found to be significantly associated with the germinal center B-cell-like DLBCL subtype. Overall, array-CGH identified relatively small genomic regions associated with outcome, which, along with follow-up expression studies, may reveal target genes important in DLBCL clinical behavior. (Blood. 2006;107:2477-2485)Keywords
This publication has 38 references indexed in Scilit:
- A microRNA polycistron as a potential human oncogeneNature, 2005
- Expression of the AID protein in normal and neoplastic B cellsBlood, 2004
- Clinicopathologic Significance and Prognostic Value of Chromosomal Imbalances in Diffuse Large B-Cell LymphomasJournal of Clinical Oncology, 2004
- Detection of large-scale variation in the human genomeNature Genetics, 2004
- Identification and Characterization of a Novel Gene, C13orf25 , as a Target for 13q31-q32 Amplification in Malignant LymphomaCancer Research, 2004
- Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomasBlood, 2004
- Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarrayBlood, 2004
- Hidden gene amplifications in aggressive B-cell non-Hodgkin lymphomas detected by microarray-based comparative genomic hybridizationOncogene, 2003
- Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphomaGenes, Chromosomes and Cancer, 2002
- Distinct types of diffuse large B-cell lymphoma identified by gene expression profilingNature, 2000