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. 2022 Feb 23;13:898. doi: 10.1038/s41467-022-28566-4

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© The Author(s) 2022, corrected publication 2022

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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Fig. 2 — a Association between recurrent somatic alterations and overall survival in acral melanoma. Shown are genes with a nonsynonymous mutation frequency ≥5% in either melanoma subtype and focal copy number events with ≥10% recurrence frequency in each cohort. |Z | > 1.96 is P < 0.05. b Overall survival of acral melanoma patients stratified by 22q11.21 amplification status. Significance was assessed with a two-sided log-rank test. HR hazard ratio. 95% HR confidence intervals are shown in brackets. c Left: Acral melanoma stage versus 22q11.21 amplification status. Significance was evaluated by a Chi-square test. Right: Fraction of 22q11.21-amplified melanomas versus lymph node status. d Hallmark pathways enriched in 22q11.21-amplified vs. non-amplified acral melanomas, as determined by pre-ranked gene set enrichment analysis. OXPHOS oxidative phosphorylation. e Hierarchical clustering of 31 immunomodulatory genes (average linkage with Euclidean distance) in acral melanomas. CD3D and CD8A are lineage markers for T cells and CD8 T cells, respectively. f Frequency of 22q11.21-amplified acral melanomas in immune clusters 1 and 2 from e. Significance was determined by Fisher’s exact test. g Top: UMAP showing CytoTRACE-inferred differentiation scores of acral melanoma cells from a 22q11.21-amplified specimen (YUJASMIN). Bottom: CytoTRACE scores (acral melanoma cells) in amplified vs. non-amplified tumors. Box center lines, bounds of the box, and whiskers indicate medians, first and third quartiles, and minimum and maximum values within 1.5×IQR (interquartile range) of the box limits, respectively. Significance was determined using a two-sided, unpaired Wilcoxon rank-sum test relative to YUJASMIN (n = 312 cells) for YUGRUS (n = 3786 cells, P = 1.21 × 10^–22), YUMASK (n = 15,006 cells, P = 4.38 × 10^–87), and YUPARK (n = 8141 cells, P = 1.06 × 10^–35). h Top: CNVs within the 22q arm of 97 acral melanomas. Genes within the minimum region of focal amplification in 22q11.21 are indicated. Columns indicate genes ordered by location. Bottom: Mean gene-level copy number change in 97 acral melanomas versus the concordance between expression and copy number for each gene. The latter is expressed as the –log₁₀ p value of a two-sided, unpaired Wilcoxon rank-sum test. Negative associations with amplification status were multiplied by –1. Only genes within the 22q11.21 focal amplification identified by GISTIC are shown (n = 24; Supplementary Table 6). Source data are provided as a Source Data file.