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-likeDLBCLsubtype. 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. © 2006 by The American Society of Hematology. |
Keywords: |
cancer chemotherapy; cancer survival; controlled study; treatment outcome; survival rate; major clinical study; clinical feature; disease classification; chromosome 12; in situ hybridization, fluorescence; cohort analysis; prediction; b cell lymphoma; germinal center; lymphoma, b-cell; correlation analysis; dna; genomics; multivariate analysis; large cell lymphoma; gene dosage; nucleic acid hybridization; anthracycline; anthracyclines; chromosome analysis; chromosome loss; chromosomes, human; comparative genomic hybridization; chromosome 2; lymphoma, large-cell, diffuse
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