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Clinicopathologic Significance and Prognostic Value of Chromosomal Imbalances in Diffuse Large B-Cell Lymphomas

From the Hematopathology Section, Laboratory of Pathology and Hematology Department, Hospital Clínic, Institut d'Investigacions Biomediques August Pi I Sunyer, University of Barcelona, Barcelona; and Information and Studies Service, Department of Health and Social Security, Barcelona, Spain

Address reprint requests to Elias Campo, Laboratory of Pathology, Hospital Clínic, Villarroel 170, 08036-Barcelona, Spain; e-mail: ecampo{at}clinic.ub.es

PURPOSE: To determine the clinicopathologic significance and prognostic value of chromosomal imbalances in diffuse large B-cell lymphomas (DLBCL).

PATIENTS AND METHODS: We have examined 64 tumors at diagnosis using comparative genomic hybridization and real-time quantitative polymerase chain reaction (PCR), single-stranded conformational polymorphism, and DNA sequencing for the analysis of several potential target genes.

RESULTS: The most recurrent alterations were gains of 18q (20%), Xq (15%), 2p, 7q, and 12p (14%), and losses of 6q and 17p (14%). Frequent high-level DNA amplifications were detected at 2p13-p16 and 18q21 loci. Real-time quantitative PCR detected REL and BCL11A gene amplifications in the nine patients with gains at 2p13-p16 and only in one additional patient with normal chromosome 2. Similarly, the BCL-2 gene was amplified in the 12 tumors with gains of 18q21 but in none of 39 patients with normal 18q profile. p53 gene inactivation was detected in nine of 58 (16%) tumors and was commonly associated with 17p losses. Tumors with 18q gains were significantly associated with a high number of chromosomal imbalances, primary nodal presentation, high serum lactate dehydrogenase levels, high International Prognostic Index, shorter cause-specific survival, and a high risk of relapse. Losses of 17p and p53 gene alterations were associated with an absence of complete response achievement.

CONCLUSION: These results suggest that DLBCLs have a characteristic pattern of genomic alterations; 18q gains or amplifications and 17p losses are associated with particular clinicopathological features and aggressive clinical behavior. Additional studies are needed to confirm these observations in larger series of patients.

Supported by grants SAF 2002/03261 from Comisión Interministerial de Ciencia y Tecnología, PI030473 from Fondo Investigación Sanitaria (FIS), Redes Temáticas de Centros de Cáncer (C03/110) y estudio de linfomas (G03/179) from FIS, Instituto de Salut Carlos III, and Generalitat de Catalunya 2000SGR00118. S.B. was supported by Fundació Internacional José Carreras (FIJC/01). M.S. was supported in part by Dakocytomation.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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