DNA methylome of MCL subtypes and its relationship with genomic alterations. (A) Overlap of cMCL and nnMCL with epigenetic subgroups on the basis of cell of origin methylation signature. (B) Principal component analysis of DNA methylation data for 70 MCL (first and second components are shown). MCL subtypes are represented as triangles or circles, whereas the color represents the proliferative history on the basis of DNA methylation of each MCL sample (epiCMIT score). (C) epiCMIT correlates with mutational signatures related to cell division, including SBS5 and SBS9 (ncAID). (D) epiCMIT correlates with the total number of driver alterations in MCL, particularly in cMCL. (E) Driver alterations associated with higher or lower epiCMIT. The 95% confidence intervals for the mean epiCMIT difference between the presence and absence of each alteration are shown. The effect in the whole cohort was adjusted by the cell of origin (C1/C2). (left) Colors depict different significant levels after false discovery rate (FDR) correction. Oncoprint with genetic alterations associated with the epiCMIT together with clinicobiological variables. (right) Patients are ordered according to the epiCMIT score, separately in the 2 MCL subtypes.