Cell of origin: concordance across studies. (A) Sequential models relating subsets of DLBCL to stages of normal B-cell development on the basis of shared transcriptional profiles. Two groups of DLBCLs were initially identified—GC-like and activated B-cell–like (ABC)—based on similarities in expression of approximately 375 genes in the tumors and normal GC B cells or in vitro–activated peripheral-blood B cells (study 1).⁷⁶  The cell-of-origin (COO) signature was subsequently revised to include only 100 genes and to identify GC- and ABC-like DLBCLs and a third group of tumors without either signature (“type 3”; study 2).⁷⁸  Using the same large data set, the COO signature was further refined to include only 27 genes, again identifying GC- and ABC-like tumors and a third unspecified category, termed “other” (study 3).⁸¹  (B) Concordance between the sequential COO models. Although the sequential 100- and 27-gene models largely identified the same tumors as GC- and ABC-like, there was poor agreement on the third category, indicating additional heterogeneity beyond the COO distinction.