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. 2020 Jan 16;11:333. doi: 10.1038/s41467-019-14085-2

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© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020

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. 1 — a Schematic depicting the experimental hypothesis: genes whose expression is upregulated in melanoblasts and metastatic melanoma, but downregulated in differentiated melanocytes (red line), may drive cellular functions that promote melanoma metastasis (MetDev genes). b Confocal imaging of iDct-GFP embryo at embryonic day 15.5 (E15.5) is magnification ×5, scale bars, 5 mm. c RNA-seq expression of mouse developing melanocytes: 467 embryo-specific genes shown. Black arrows: 42 genes identified from Cox proportional hazards model. Green arrows: genes functionally validated. Red arrow: Kdelr3. Kdelr3 validated both in Cox proportional hazards model and functionally validated. Embryonic days 15.5 and 17.5 (E15.5 and E17.5, respectively). Postnatal day 1 and postnatal day 7 (P1, P7, respectively). d RNA-seq expression of 46 genes in mouse developing melanocytes: Black text: 42 genes identified from Cox proportional hazards model. Red text: four genes functionally validated. Kdelr3 validated both in Cox proportional hazards model and functionally validated. e, f Cox proportional hazards modeling (GSE19234) yielded a 43-gene MetDev signature. Patients’ risk assessed in GSE8401 patient cohort. Late stage: stage III/IV metastatic melanomas. Early stage: stage I/II primary tumors. High expression: high expression of gene signature. Low expression: low expression of gene signature. Log-rank test. Late stage, high (N = 23) vs. low (N = 24), P = 3.486e − 05. Early stage, high (N = 14) vs. low (N = 13), P = 0.7655. c, d Color scales represent gene expression z scores.