DLBCL-type RT appears to lack some of the genetic alterations seen in DLBCL, NOS such as inactivation of CREBBP/EP300, B2M, and translocations of BCL2 or BCL6. Recent genomic studies have shown that RT DLBCL integrates alterations in cell cycle regulators (90% of cases) (TP53, CDKN2A/B, CDKN1B), chromatin modifiers (79%) (SETD2, ARIDA/B), MYC (74%), NF-κB (74%) (BIRC3, TNFAIP3, NFKBIE), and NOTCH (32%) (NOTCH1, SPEN) pathways with most of these aberrations simultaneously present in most cases with the exception of MYC and NOTCH alterations that tend to occur in different tumours [36, 41, 42]. This evidence concerns the gene SPEN and diffuse large B-cell lymphoma.