In the present study, we used a validated canine BCL in vitro model, i.e. the CLBL-1 cell line [28], to investigate the methylation-dependent regulation of four TSGs, namely the Homeobox D10 (HOXD10), the Fibroblast Growth Factor Receptor 2 (FGFR2), the Inter-Alpha-Trypsin Inhibitor Heavy Chain Family Member 5 (ITIH5) and the RAS Protein Activator Like 3 (RASAL3); these genes have been shown to be hypermethylated in canine diffuse large B-cell lymphoma (DLBCL) [29]. Here, ITIH5 is linked to diffuse large B-cell lymphoma.