Development of human EBV⁺-DLBLs from PDXs of gastric cancers. (A) Timeline of the development of EBV⁺-DLBL, LPD with marked T-cell expansion, and gastric adenocarcinoma in 59 gastric cancer PDX mouse models. Engrafted tumors were considered to have graduated when the tumors reached about 1000 mm³ in size. (B) Immunohistological analysis of EBV⁺-DLBL and EBV⁺-LPD that developed in gastric cancer PDXs. Brown color indicates a positive result for CD20, CD3, Ki-67, and EBV-encoded RNA (EBER). All developed lymphomas were CD20-positive, showed high proliferation based on the Ki-67 labeling index (> 95%), and were judged EBV-positive by in situ hybridization. All LPDs showed rich CD3-positive lymphocyte infiltration with a few EBV-positive B cells. (C) Lymphoma cells showed diffuse positivity for immunoglobulin κ chain, but negativity for λ chain in immunohistochemistry. (D) Lymphoma showed clonal proliferation in the IgH gene rearrangement test. (E) Somatic mutation profiles of 59 PDX samples and 48 DLBLs from the TCGA database. Genes marked in red text are frequently altered in Burkitt lymphoma. (F) Mutation signatures observed in EBV⁺-DLBL and gastric adenocarcinoma PDX samples. The x-axes represent each sample and were ordered according to the total number of somatic substitutions (y-axes). Contributions of each mutational signature are shown as bar graphs.