Comparative genome-wide profiling of post-transplant lymphoproliferative disorders and diffuse large B-cell lymphomas

Andrea Rinaldi, Ivo Kwee, Giulia Poretti, Afua Mensah, Giancarlo Pruneri, Daniela Capello, Davide Rossi, Emanuele Zucca, Maurilio Ponzoni, Carlo Catapano, Maria Grazia Tibiletti, Marco Paulli, Gianluca Gaidano, Francesco Bertoni

Research output: Contribution to journalArticlepeer-review

Abstract

Post-transplant lymphoproliferative disorders (PTLD) are a major complication of solid organ transplantation, representing a cause of severe morbidity and mortality. Apart from Epstein-Barr virus infection, knowledge of the pathogenesis of monoclonal PTLD is limited. Powerful analysis techniques, such as whole genomic DNA profiling (array comparative genomic hybridisation), can improve our understanding of PTLD pathogenesis. Whole genome profiling using the Affymetrix GeneChip Human Mapping 10 k 2.0 was performed on 20 PTLD cases and 25 cases of diffuse large B-cell lymphoma (DLBCL) from immunocompetent patients as a control group. Recurrent lesions were detected among all the samples. Chromosome 18q, 7q, 3q and 12 were the most common gains in the control group. Chromosomes 5p and 11p were commonly gained in PTLD-DLBCL. The latter had frequent losses of 6q, 17p, 1p and 9p. Chromosome 12p was the most frequent target of deletions among PTLD-DLBCL cases. Loss of heterozygosity (LOH) did not always match DNA loss: chromosome 10 seemed to be targeted by uniparental disomy in PTLD. Small deletions and gains, involving both known (BCL2 and PAX5) and unknown genes (ZDHHC14), were identified. These data suggest that PTLD share, at a lower frequency, common genetic aberrations with DLBCL from immunocompetent patients. The demonstration of 9p13 amplification emphasises the importance of PAX5 in PTLD. The combination of DNA copy number and LOH assessment lead to the hypothesis that uniparental disomy may be a potential mechanism in B-cell lymphomagenesis.

Original languageEnglish
Pages (from-to)27-36
Number of pages10
JournalBritish Journal of Haematology
Volume134
Issue number1
DOIs
Publication statusPublished - Jul 2006

Keywords

  • Affymetrix
  • ArrayCGH
  • Burkitt's lymphoma
  • Diffuse large B cell lymphoma
  • Post-transplant lymphoproliferative disorder

ASJC Scopus subject areas

  • Hematology

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