Fig. 4: Normal tissue-depleted transcriptomic signatures of organ-specific metastases.

a, PCA of transcriptional profiles of RAM tumors (n = 93) colored by organ sites, RAM cases and treatment histories. b, DGS analyses of tumor-cell-enriched, organ-specific transcriptomes. DGSs between tumors of organ A versus other organs (that is, B, C, D, E and F) are identified by GSEA. DGSs are similarly identified between NAN tissues (n = 67) of organ A versus other organs. Subtraction of the latter from the former identifies normal-corrected/depleted (or tumor-cell-enriched) DGSs of organ-specific transcriptomes. c, Normalized enrichment scores (NESs) of top five positively and negatively enriched gene sets (hallmark gene sets, Molecular Signatures Database) in organ-specific metastases of therapy-resistant cutaneous melanoma from rapid autopsies. d,e, Immunofluorescent staining of indicated proteins within tumor tissues of distinct organs from two RAM cases (ruler, 50 μm; experiment performed once). PC, principal component.