Array comparative genomic hybridization reveals genomic copy number changes associated with outcome in diffuse large B-cell lymphomas
| Autor: | Jeffrey L. Halaas, Seeta R. Chaganti, Gouri Nanjangud, Julie Teruya-Feldstein, Ennapadem S. Venkatraman, Weiyi Chen, Andrew D. Zelenetz, Jane Houldsworth, R. S. K. Chaganti, Adam B. Olshen |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Lymphoma
B-Cell Immunology Gene Dosage Biology Biochemistry Gene dosage medicine Chromosomes Human Humans Anthracyclines Survival rate Gene Chromosome 12 In Situ Hybridization Fluorescence Neoplasia Germinal center Chromosome Nucleic Acid Hybridization Cell Biology Hematology medicine.disease Molecular biology Lymphoma Survival Rate Treatment Outcome Lymphoma Large B-Cell Diffuse Comparative genomic hybridization |
| Popis: | 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) |
| Databáze: | OpenAIRE |
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