Genomic aberrations affecting the outcome of immunodeficiency-related diffuse large B-cell lymphoma

Abstract

The objective of this study was to evaluate the prognostic impact of genomic regions in a series of human immunodeficiency virus (HIV)-related diffuse large B-cell lymphomas (HIV-DLBCLs) and post-transplant DLBCLs (PT-DLBCLs) analyzed by genome-wide DNA profiling. Minimal common regions (MCRs) were estimated on genomic profiles obtained using Affymetrix Human Mapping 250k Nsp I arrays and tested for their impact on clinical outcome by univariate analysis on 36 PT-DLBCLs, 19 HIV-DLBCLs and, as a control group, 149 DLBCLs arising in immunocompetent individuals (IC-DLBCLs). PT-DLBCL and HIV-DLBCL presented a similar outcome. Immunodeficiency-related DLBCL (ID-DLBCL) had a worse overall survival (OS) than IC-DLBCL. Seven MCRs showed a statistical impact on OS in PT-DLBCL and four in HIV-DLBCL. Among these, the presence of gains at 1q or at 18q defined a group of patients with PT-DLBCL with a very poor outcome (p < 0.0001). The presence of del(3p14.2) or of + 2p23.1 identified a group of HIV-DLBCLs with a very poor outcome (p = 0.0072). It was concluded that genomic aberrations affecting outcome differ between ID-DLBCL and IC-DLBCL and are also dependent on the type of acquired immunodeficiency.

Keywords::

• HIV
• organ transplant
• lymphoma
• outcome
• immunodeficiency
• diffuse large B-cell lymphoma
• FHIT

Acknowledgements

We would like to thank our colleagues Michael Mian, Michela Boi (Bellinzona, Switzerland), Alessandro Rambaldi (Bergamo, Italy), Marcello Gambacorta, Enrica Morra, Maurilio Ponzoni, Andrés J. M. Ferreri, Luca Baldini (Milan, Italy), Giorgio Inghirami (Turin, Italy), Miguel A. Piris (Madrid, Spain) and Fabio Facchetti (Brescia, Italy) for providing additional material and clinical information; and Afua Adjeiwaa Mensah (Bellinzona, Switzerland) for manuscript editing.

This work was supported by: Oncosuisse grant OCS-1939-8-2006; Swiss National Science Foundation (grants 205321-112430, 205320-121886/1); Cantone Ticino (“Computational life science/Ticino in rete” program); Fondazione per la Ricerca e la Cura sui Linfomi (Lugano, Switzerland); Ricerca Sanitaria Finalizzata 2008 and 2009, Regione Piemonte, Torino, Italy; VI Programma Nazionale di Ricerca sull'AIDS, ISS, Rome, Italy; Novara-AIL Onlus; PHS grant, UO1 CA 114778.

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