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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2477-2485.
Prepublished online as a Blood First Edition Paper on November 29, 2005; DOI 10.1182/blood-2005-07-2950.
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NEOPLASIA
Array comparative genomic hybridization reveals genomic copy number changes associated with outcome in diffuse large B-cell lymphomas
Weiyi Chen,
Jane Houldsworth,
Adam B. Olshen,
Gouri Nanjangud,
Seeta Chaganti,
Ennapadem S. Venkatraman,
Jeffrey Halaas,
Julie Teruya-Feldstein,
Andrew D. Zelenetz, and
R. S. K. Chaganti
From the Cell Biology Program, the Departments of Medicine, of Epidemiology and Biostatistics, and of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
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)
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