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. 2023 Apr 27;29(5):1123–1134. doi: 10.1038/s41591-023-02304-9

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 2 — (a) Somatic copy-number alterations of the RAM cohort (n = 74 tumors) (left). Outermost layer, chromosomal regions; second layer, heatmap of G scores (GISTIC 2.0); third layer, P values of amplified and deleted regions (red dots indicate significance); innermost layer, frequencies of amplified and deleted regions; arrows, locations of functionally important genes displaying significant amplification (red) or deletion (blue). (b) Top 50 significantly altered exomic regions by GISTIC analysis, listed in decreasing order of recurrence and annotated with associated genes, across RAM cases/patients, organ sites, and treatment histories. AMP, amplification; DEL, deletion. (c) Venn diagrams showing overlaps between (i) significantly amplified (left) or deleted (right) genes based on GISTIC2.0 analysis of the RAM tumors and (ii) frequency-enriched, copy number alterations observed in RAM tumors versus TCGA–SKCM tumors (BRAF- and NRAS-mutant only). (d) The numbers and proportions of significantly mutated genes (SMGs) with no expression (mean log₂CPM < 0), expresssion (0 ≤ mean log₂CPM < 4), or high expression (mean log₂CPM > 4) among RAM tumors. (e) Venn diagram of overlapping SMGs identified in three tumor cohorts: (i) RAM, (ii) clinical post-MAPKi-only (pre-MAPKi SMGs subtracted) and, (iii) clinical post-ICB-only (pre-ICB SMGs subtracted). (f) Top 20 significantly enriched biological processes of SMGs with expression (as defined in d). One-sided Fisher’s exact test without multiple comparisons. (g) Venn diagrams showing overlapping numbers of SMGs identified in the RAM tumor cohort versus SMGs identified in published (PMIDs shown) large-scale melanoma and pan-cancer cohorts. P values by one-sided hypergeometric test. (h) Venn diagrams showing overlapping numbers of SMGs identified in published pan-cancer (top) or melanoma (bottom) cohorts.

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