Array comparative genomic hybridization identifies genetic regions associated with outcome in aggressive diffuse large B-cell lymphomas.
BACKGROUND
Diffuse large B-cell lymphomas (DLBCLs) are the most common type of non-Hodgkin lymphomas. With chemotherapy and progenitor stem cell transplantation, about 60% of patients with DLBCL are long-term survivors. The International Prognostic Index identifies patients with different outcomes. However, biologic characteristics also may help to discriminate different treatments groups.


METHODS
DNA copy number changes identified by array comparative genomic hybridization (array-CGH) were studied in 40 patients who had DLBCL with a poor prognosis and who were treated uniformly with dose-escalated cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and intensification before high-dose chemotherapy with autologous stem cell transplantation.


RESULTS
In total, 722 copy number changes were observed (median, 5 copy number changes per patient; range, 0-75 copy number changes per patient), with a predominance of gains. Gains on 2p16 were present only in patients who failed to achieve a complete response after escalated CHOP therapy (P < .05). In univariate analysis, gains on 2p16 and losses on 17p13 (the tumor protein p53 gene TP53 gene) were associated with a poor response to the therapy. Furthermore, age >60 years and losses on 10q23.31 (the phosphatase and tensin homolog gene PTEN) or on 17p13 were associated with short survival. In multivariate analysis, only advanced age and losses on 10q23.31 retained an adverse prognostic impact.


CONCLUSIONS
Array-CGH identified multiple regions with common copy number changes, some of which were associated with outcome in patients with DLBCL.
Robledo
Cristina
C
Institute of Molecular and Cellular Biology of Cancer, Cancer Research Center, University of Salamanca, Salamanca, Spain.
García
Juan L
JL
Caballero
Dolores
D
Conde
Eulogio
E
Arranz
Reyes
R
Flores
Teresa
T
Grande
Carlos
C
Rodríguez
José
J
García
Eva
E
Sáez
Ana I
AI
González
Marcos
M
Gutiérrez
Norma C
NC
Piris
Miguel A
MA
Hernández
Jesús M
JM
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D055028:Comparative Genomic Hybridization; D003520:Cyclophosphamide / Q000627:therapeutic use; D004247:DNA / Q000032:analysis; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D018628:Gene Dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000628:therapy; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D004247:DNA; D011241:Prednisone