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. 2020 Jan 3;11:84. doi: 10.1038/s41467-019-13847-2

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© The Author(s) 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 Kaplan–Meier survival curves of Lgr5^{eGFP−Ires−CreERT2}Trp53^loxP/loxPRb1^loxP/loxPAi9 mice with (Trp53^−/−Rb1^−/−, n = 42) and without (Control, n = 9) tamoxifen treatment (log-rank test P < 0.0001), and Lgr5^{eGFP−Ires−CreERT2}Trp53^loxP/loxPAi9 (Trp53^−/−, n = 11) mice and Lgr5^{eGFP−Ires−CreERT2}Rb1^loxP/loxPAi9 mice (Rb1^−/−, n = 8) treated with tamoxifen (P < 0.001 vs Trp53^−/−Rb1^−/− mice for both Trp53^−/− and Rb1^−/−). b tdTomato-expressing (tdTomato⁺) neoplastic masses (red, arrows) in the stomach of Lgr5^{eGFP−Ires−CreERT2}Trp53^loxP/loxPRb1^loxP/loxP Ai9 mouse 291 days post induction (p.i.) with tamoxifen. Bright field (left) and fluorescence (right). The punctate lines indicate SCJ line. F forestomach, E esophagus, C corpus, A antrum. c Distribution of neoplasms in stomach regions (n = 20). d, e SCJ between the squamous (SE) and glandular (GE) epithelium in adult Lgr5^{eGFP−Ires−CreERT2}Trp53^loxP/loxPRb1^loxP/loxPAi9 mouse without tamoxifen induction. Rectangle in d indicates area shown in e. SCJ carcinogenesis in Lgr5^{eGFP−Ires−CreERT2}Trp53^loxP/loxPRb1^loxP/loxPAi9 mice includes dysplastic glandular lesions (f, arrow, 120 days p.i.), early carcinoma (g, arrow, 177 days p.i.), and advanced carcinoma (h, arrow, 239 days p.i.) with vascular invasion (i). Preferential location of SCJ carcinoma metastases in the lymph node (j, 20% of cases) and the liver (k 35% of cases). Rectangle in top images indicates areas shown in bottom images. l Gene Set Enrichment Analysis of RNA-seq data of mouse gastric SCJ cancers (n = 5) using human gastroesophageal cancer signature genes⁷⁰. Enrichment score (ES) = 0.46, normalized enrichment score (NES) = 1.38, false discovery rate (FDR) q value = 0.08, P < 0.05. d–k Hematoxylin and eosin staining. Scale bar in k represents 3 mm (b), 1 mm (d and h), 60 μm (e), 40 μm (f), 300 μm (g), 100 μm (i), 600 μm (j top panel), 100 μm (j bottom panel), 4.5 mm (k top panel), and 175 μm (k bottom panel). Source data are provided as a Source Data file.