Comparison of mutational profiles between EMD and BMA samples. (A) Cancer cell fraction (CCF) analysis of commonly mutated genes in EMD samples reveals that mutations in NRAS, KRAS, and BRAF exhibit clonal patterns in ∼50% of cases. (B) The CCF of select genes mutated in EMD and BMAs are demonstrated. In BMAs, mutations in NRAS, KRAS, and BRAF are less likely to be clonal compared to their counterparts in EMD samples. (C) TMB is significantly elevated in EMD samples compared to BMA samples collected at the same time point as EMD development (r = 0.63; P = .0001). (D) No significant difference in TMB is observed between de novo (previously untreated) and secondary (posttreatment) EMD samples (r = 0.16; P = .5). (E) Among mutational pathways, alterations in the MAPK pathway are the most frequent, occurring in 94% of EMD samples vs 60% in BMAs (P = .02). Other frequently affected pathways in EMD include transcriptional machinery (83%), chromatin histone modifiers (78%), RNA abundance (72%), and immune signaling (66%).