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. 2021 Jun;35(11-12):870–887. doi: 10.1101/gad.348316.121

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© 2021 Norton et al.; Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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Figure 4. — Transcriptional analysis of MLN4924-treated tumors identify changes in neuroendocrine signature in high-grade neuroendocrine cancers (A,B) Volcano plots of edgeR analysis results from RNA-seq performed on five MLN4924-treated and five vehicle-treated JHU-LX108 (A) or MSK-LX227C (B) PDX tumors. Green markers indicate select neuroendocrine genes and blue markers indicate select NRF2 targets. (C) Venn diagram showing common significant down-regulated genes (FDR < .05) determined by edgeR analysis of MLN4924-treated JHU-LX108 and MSK-LX227C PDX tumors. Notable common genes highlighted in inset. (D) Gene set enrichment analysis plots for treated JHU-LX108 (top) and MSK-LX227C (bottom) tumors using list of identified ASCL1 direct targets in SCLC. (E) Venn diagram showing common significant up-regulated genes (FDR < .05) determined by edgeR analysis of MLN4924-treated JHU-LX108 and MSK-LX227C PDX tumors. Notable common genes highlighted in the inset. (F) Gene set enrichment analysis plots for treated JHU-LX108 (top) and MSK-LX227C (bottom) tumors using list of NRF2 targets. (G) Heat map of select differentially expressed neuroendocrine signature genes for MLN4924-treated JHU-LX108 or MSK-LX227C PDX tumors compared with vehicle treatment. Color indicates Z-score for each comparison (five vehicle vs. five MLN4924).