Fig. 1: Whole-exomic landscape of therapy-resistant cutaneous melanoma.
a, Tumor somatic mutational burdens based on synonymous and non-synonymous IDs and SNVs across RAM cases (patients), organ sites and treatment histories. b, Venn diagrams showing overlaps of significantly amplified (left) or deleted (right) genes based on frequency-enriched CNAs observed in three comparative cohorts: (1) RAM tumors versus TCGA–SKCM tumors (BRAF mutant and NRAS mutant only); (2) MAPKi-only post versus pre tumors; and (3) ICB-only post versus pre tumors. c, Highly expressed SMGs in the RAM tumor cohort annotated by mutational types, cases, organ sites and treatment histories. Yellow highlights, SMGs identified by prior published studies (Extended Data Fig. 2g,h). Underlines, SMGs significantly (two-sided Fisher’s exact test, FDR-adjusted P < 0.05) enriched in the RAM tumor cohort (versus the TCGA–SKCM tumor cohort, BRAF mutant and NRAS mutant only). MYO9B, P = 7.97 × 10−5 and adjusted P = 0.004144; B2M, P = 1.75 × 10−3 and adjusted P = 0.044013; PRSS27, P = 2.12 × 10−3 and adjusted P = 0.044013. d,e, Copy number and mutational (missense, nonsense, splice-site, frame-shift IDs) status of overlapping amplified (d) or deleted (e) genes (b and Extended Data Fig. 2c). f, Ratios of variant versus normal allele frequencies in eight overlapping amplified genes (BRAF, n = 39; CREB3L2, n = 7; KEL, n = 15; MGAM, n = 9; RAD51B, n = 5; RELN, n = 26; SETD1B, n = 6; TERT, n = 5 tumors). Central line of each box, median; top and bottom edges of each box, first and third quartiles; whiskers extend 1.5× the interquartile range beyond box edges. g, Copy number and mutational status of the overlapping SMG B2M (Extended Data Fig. 2e) in the RAM cohort (left); ID signatures identified among B2M-mutated RAM tumors (right). del, deletion; ins, insertion; SNP, single-nucleotide polymorphism.
