Array comparative genomic hybridization reveals genomic copy number changes associated with outcome in diffuse large B-cell lymphomas.
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.
Chen
Weiyi
W
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Houldsworth
Jane
J
Olshen
Adam B
AB
Nanjangud
Gouri
G
Chaganti
Seeta
S
Venkatraman
Ennapadem S
ES
Halaas
Jeffrey
J
Teruya-Feldstein
Julie
J
Zelenetz
Andrew D
AD
Chaganti
R S K
RS
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
D018943:Anthracyclines