SHM hotspots have been observed at non-immunoglobulin loci, particularly within the 5′ regulatory regions of certain proto-oncogenes (BCL6, MYC, PAX5, PIM1, RhoH, S1PR2, and SOCS1) in diffuse large B cell lymphomas (DLBCL) [10], [11], [12], an aggressive disease comprising approximately 40% newly diagnosed non-Hodgkins lymphomas [13]. This evidence concerns the gene S1PR2 and diffuse large B-cell lymphoma.