Single nucleotide polymorphism-arrays provide new insights in the pathogenesis of post-transplant diffuse large B-cell lymphoma

Andrea Rinaldi, Daniela Capello, Marta Scandurra, Timothy C. Greiner, Wing C. Chan, Govind Bhagat, Davide Rossi, Enrica Morra, Marco Paulli, Alessandro Rambaldi, Paola M V Rancoita, Giorgio Inghirami, Maurilio Ponzoni, Santiago M. Moreno, Miguel A. Piris, Michael Mian, Ekaterina Chigrinova, Emanuele Zucca, Riccardo D. Favera, Gianluca GaidanoIvo Kwee, Francesco Bertoni

Research output: Contribution to journalArticlepeer-review

Abstract

Post-transplant lymphoproliferative disorders (PTLD) are complications of solid organ transplantation associated with severe morbidity and mortality. Diffuse large B-cell lymphoma (DLBCL) represents the most common form of monomorphic PTLD. We studied 44 cases of post-transplant DLBCL (PT-DLBCL) with high-density genome wide single nucleotide polymorphism-based arrays, and compared them with 105 cases of immunocompetent DLBCL (IC-DLBCL) and 28 cases of Human Immunodeficiency Virus-associated DLBCL (HIV-DLBCL). PT-DLBCL showed a genomic profile with specific features, although their genomic complexity was overall similar to that observed in IC- and HIV-DLBCL. Among the loci more frequently deleted in PT-DLBCL there were small interstitial deletions targeting known fragile sites, such as FRA1B, FRA2E and FRA3B. Deletions at 2p16.1 (FRA2E) were the most common lesions in PT-DLBCL, occurring at a frequency that was significantly higher than in IC-DLBCL. Genetic lesions that characterized post-germinal center IC-DLBCL were under-represented in our series of PT-DLBCL. Two other differences between IC-DLBCL and PT-DLBCL were the lack of del(13q14.3) (MIR15/MIR16) and of copy neutral LOH affecting 6p [major histocompatibility complex (MHC) locus] in the latter group. In conclusion, PT-DLBCL presented unique features when compared with IC-DLBCL. Changes in PT-DLBCL were partially different to those in HIV-DLBCL, suggesting different pathogenetic mechanisms in the two conditions linked to immunodeficiency.

Original languageEnglish
Pages (from-to)569-577
Number of pages9
JournalBritish Journal of Haematology
Volume149
Issue number4
DOIs
Publication statusPublished - May 2010

Keywords

  • Affymetrix
  • Comparative genomic hybridization
  • Diffuse large B-cell lymphoma
  • Human immunodeficiency virus
  • Immunodeficiency
  • Solid organ transplant

ASJC Scopus subject areas

  • Hematology

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