Extended Data Fig. 5: Gastric EPO-GEMM tumors originate from epithelial cells in the stomach.
From: Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease
(a) Kaplan–Meier survival curves of C57BL/6 EPO-GEMMs after electroporation with either MYC and Pten−/− vectors (blue, n = 9 mice) or MYC vector only (black, n = 4 mice). (b–e) Representative H&E (B) and immunohistochemistry staining for E-Cadherin (E-cad) (C), Ki67 (D), and hydrogen/potassium ATPase (H+K) (E) of a MYC-Pten EPO-GEMM gastric tumor. (f) Schematic of CK8-Cre restricted EPO-GEMM experiments. A transposon vector harboring MYC in combination with a Sleeping Beauty transposase (SB13) and/or a CRISPR-Cas9 vector targeting either p53 or Apc were delivered into the stomach of CK8-CreERT2; LSL-Cas9 mice by direct in vivo electroporation. (g) Kaplan–Meier survival curves of C57BL/6 MYC-p53−/− EPO-GEMMs (blue dashed line, n = 9 mice, same cohort as shown in Fig. 2a) or CK8-CreERT2; LSL-Cas9 MYC-p53−/− EPO-GEMMs (blue line, n = 7 mice). (h) Kaplan–Meier survival curves of C57BL/6 MYC-Apc−/− EPO-GEMMs (green dashed line, n = 10 mice, same cohort as shown in Fig. 2c) or CK8-CreERT2; LSL-Cas9 MYC-Apc−/− EPO-GEMMs (green line, n = 6 mice). (i-j) H&E (I) and immunohistochemistry for E-cadherin (E-Cad) (J) of a CK8-CreERT2; LSL-Cas9 MYC-Apc−/− EPO-GEMM gastric tumor. Representative images of n = 4 mice. (k) Schematic of Atp4b-Cre restricted EPO-GEMM experiments. A transposon vector harboring MYC in combination with a Sleeping Beauty transposase (SB13) and/or a CRISPR-Cas9 vector targeting either p53 or Apc were delivered into the stomach of Atp4b-Cre; LSL-Cas9 mice by direct in vivo electroporation. (l-m) H&E of an Atp4b-Cre; LSL-Cas9 MYC-Apc−/− EPO-GEMM gastric tumor (L) and a corresponding liver metastasis (M) (scale bar = 1 mm upper row, 200 µm lower row). Representative images of n = 2 mice. (n-o) H&E of an Atp4b-Cre; LSL-Cas9 MYC-p53−/− EPO-GEMM gastric tumor (N) and a corresponding lung metastasis (O) (scale bar = 1 mm upper row, 200 µm lower row). Representative images of n = 2 mice. (p) Sparse whole-genome sequencing analysis of copy number alterations in MYC-Cdh1 gastric EPO-GEMM tumors (n = 4 mice). Frequency plot is shown on the top and individual sample tracks are provided on the bottom. (q) Sparse whole-genome sequencing analysis of copy number alterations in MYC-Pten gastric EPO-GEMM tumors (n = 5 mice). Frequency plot is shown on the top and individual sample tracks are provided on the bottom. Statistical analysis: (G, H) one-sided log-rank test.
