Fig. 3: Somatic loss of Msh2 induces microsatellite instability gastric cancer in mice.
From: Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease
a, Kaplan–Meier survival curves of C57BL/6 EPO-GEMMs with either MYC-p53−/− (MSS; same cohort as shown in Fig. 2a; blue, n = 9 mice) or MYC-p53−/−-Msh2−/− (MSI; red, n = 11 mice) gastric cancer. b, Immunohistochemical staining for E-cadherin and Msh2 of MYC-p53−/− (MSS) or MYC-p53−/−-Msh2−/− (MSI) gastric EPO-GEMM tumors. Representative of n = 11 mice. c, WES analysis of somatic mutations per Mb in either MYC-p53−/− or MYC-p53−/−-Msh2−/− gastric EPO-GEMM tumors (n = 3 independent mice each). SNP, single-nucleotide polymorphism; INS, insertion; DEL, deletion. d, Base substitution signature in MYC-p53−/− (MSS) and MYC-p53−/−-Msh2−/− (MSI) gastric EPO-GEMM tumors (n = 3 independent mice each). e, Representative immunofluorescence staining of intratumoral regions of MYC-p53−/− (MSS) or MYC-p53−/−-Msh2−/− (MSI) gastric EPO-GEMM tumors for CD45 (red, top) or CD3 (red, bottom). Quantification to the right (n = 6 independent mice each). Data are presented as mean ± s.e.m. f, Kaplan–Meier survival curves of C57BL/6 gastric cancer EPO-GEMMs of either MYC-p53−/− genotype (left) (n = 14 IgG-treated mice and n = 15 9H10-treated mice) or MYC-p53−/−-Msh2−/− genotype (right) (n = 14 IgG-treated mice and n = 16 9H10-treated mice) after antibody-mediated blockade of CTLA-4 (9H10, 200 µg) (solid line) or IgG control (dashed line). Treatment was initiated (day 0) after tumor formation was confirmed by abdominal palpation. Statistical analyses were one-sided log-rank test (a,f) and unpaired t-test (e). NS, not significant; *P <0.05.
