Cellular origin and genetic lesions associated with distinct DLBCL subtypes. Schematic representation of the GC reaction, and its relationship with the 2 molecular subtypes of DLBCL NOS, GCB-DLBCL, and ABC-DLBCL (unclassified DLBCL not shown). The most common, functionally characterized genetic alterations identified in this disease (including those shared across different subtypes and those subtype specific) are shown in the bottom panels, where blue indicates loss-of-function events and red indicates gain-of-function events; color codes on the left denote distinct categories, according to the subverted biological pathway. Ag, antigen; Amp, amplifications; D, deletions; FDC, follicular dendritic cells; M, mutations; Tx, chromosomal translocations. Note that, at lower frequencies, mutations affecting CARD11, TNFAIP3, and MYD88 residues other than the L265 hotspot can also be observed in GCB-DLBCL. CREBBP mutations can be found in all subtypes, although frequencies are significantly higher in GCB- (30%) than ABC- (15%) DLBCL. Modified from Pasqualucci and Dalla-Favera¹³⁵  with permission.