title: Array comparative genomic hybridization reveals genomic copy number changes associated with outcome in diffuse large B-cell lymphomas.
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.
authors.affiliation: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Chen
authors.forename: Jane
authors.initials: J
authors.lastname: Houldsworth
authors.forename: Adam B
authors.initials: AB
authors.lastname: Olshen
authors.forename: Gouri
authors.initials: G
authors.lastname: Nanjangud
authors.forename: Seeta
authors.initials: S
authors.lastname: Chaganti
authors.forename: Ennapadem S
authors.initials: ES
authors.lastname: Venkatraman
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Halaas
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.forename: R S K
authors.initials: RS
authors.lastname: Chaganti
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use; D002877:Chromosomes, Human; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D009693:Nucleic Acid Hybridization / Q000379:methods*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines