Mutational landscape of B‐cell post‐transplant lymphoproliferative disorders

Summary It is currently unclear whether post‐transplant diffuse large B‐cell lymphomas ( PT ‐ DLBCL ) display a similar genomic landscape as DLBCL in immunocompetent patients ( IC ‐ DLBCL ). We investigated 50 post‐transplant lymphoproliferative disorders ( PTLD s) including 37 PT ‐ DLBCL samples for somatic mutations frequently observed in IC ‐ DLBCL . Targeted Next Generation Sequencing ( NGS ) using the Ion Torrent platform and a customized panel of 68 genes was performed on genomic DNA . Non‐tumoural tissue was sequenced to exclude germline variants in cases where available. A control cohort of 76 IC ‐ DLBCL was available for comparative analyses. In comparison to IC ‐ DLBCL s, PT ‐ DLBCL showed more frequent mutations of TP 53 ( P = 0·004), and absence of ATM and B2M mutations ( P = 0·004 and P = 0·016, respectively). In comparison to IC ‐ DLBCL s, Epstein–Barr virus ( EBV ) + PT ‐ DLBCL had fewer mutated genes ( P = 0·007) and particularly fewer mutations in nuclear factor‐κB pathway‐related genes ( P = 0·044). TP 53 mutations were more frequent in EBV ‐ PT ‐ DLBCL as compared to IC ‐ DLBCL ( P = 0·001). Germinal centre B cell ( GCB ) subtype of PT ‐ DLBCL had fewer mutations and mutated genes than GCB ‐ IC ‐ DLBCL s ( P = 0·048 and 0·04 respectively). Polymorphic PTLD displayed fewer mutations as compared to PT ‐ DLBCL ( P = 0·001). PT ‐ DLBCL differs from IC ‐ DLBCL with respect to mutations in genes related to DNA damage control and immune‐surveillance, and EBV association is likely to have a bearing on the mutational pattern.