title: Comparative genome-wide profiling of post-transplant lymphoproliferative disorders and diffuse large B-cell lymphomas.
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.
authors.affiliation: Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rinaldi
authors.forename: Ivo
authors.initials: I
authors.lastname: Kwee
authors.forename: Giulia
authors.initials: G
authors.lastname: Poretti
authors.forename: Afua
authors.initials: A
authors.lastname: Mensah
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.forename: Daniela
authors.initials: D
authors.lastname: Capello
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Carlo
authors.initials: C
authors.lastname: Catapano
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Tibiletti
authors.forename: Marco
authors.initials: M
authors.lastname: Paulli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
mesh_terms: D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006801:Humans; D007121:Immunocompetence; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D016393:Lymphoma, B-Cell / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016377:Organ Transplantation / Q000009:adverse effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction