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

Summary 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.