Single nucleotide polymorphism-arrays provide new insights in the pathogenesis of post-transplant diffuse large B-cell lymphoma.
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.
Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.
Andrea
A
Rinaldi
Daniela
D
Capello
Marta
M
Scandurra
Timothy C
TC
Greiner
Wing C
WC
Chan
Govind
G
Bhagat
Davide
D
Rossi
Enrica
E
Morra
Marco
M
Paulli
Alessandro
A
Rambaldi
Paola M V
PM
Rancoita
Giorgio
G
Inghirami
Maurilio
M
Ponzoni
Santiago M
SM
Moreno
Miguel A
MA
Piris
Michael
M
Mian
Ekaterina
E
Chigrinova
Emanuele
E
Zucca
Riccardo D
RD
Favera
Gianluca
G
Gaidano
Ivo
I
Kwee
Francesco
F
Bertoni
D055028:Comparative Genomic Hybridization; D004273:DNA, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D016867:Immunocompromised Host; D019656:Loss of Heterozygosity; D016483:Lymphoma, AIDS-Related / Q000235:genetics / Q000276:immunology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D016377:Organ Transplantation / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence
D004273:DNA, Neoplasm