Extended Data Fig. 1: Characterization of the KC-shSmad4 mouse model.
(a) Overall (pie chart) and organ-specific (stacked bar graph) frequency of metastasis in KC-shSmad4 mice. (b) Macroscopic images of tumor-bearing pancreas, liver, and lungs from KC-shSmad4 mice ( + Dox) at endpoint. Fluorescent images match the corresponding brightfield images. Data are representative of 10 (pancreas), 6 (liver), and 3 (lungs) independent mice. (c) Immunohistochemistry (IHC) staining for SMAD4 in primary and metastatic KC-shSmad4 tumors ( + Dox). Dashed lines demarcate metastases. Data are representative of 3 independent mice. (d) sWGS analysis of genome-wide copy number alterations in KC-shSmad4 primary tumor-derived cell lines (n = 10 independent mice). Frequency plot is shown on the top and individual sample tracks are provided on the bottom. (e) sWGS analysis of genome-wide copy number alterations in KC-shSmad4 tumor-derived cell lines from matched primary tumors, liver and lung metastases. The Kras and Cdkn2a/b loci are highlighted (arrows). Data are representative of 3 independent mice. (f) Frequency of the indicated homozygous deletions in SMAD4-altered (mutated or homozygously deleted, n = 959) or wild-type (WT, n = 3188) PDAC tumors in the MSK-IMPACT cohort (CDKN2A/B, p < 10−10; q < 10−10). CDKN2A/B and their adjacent gene MTAP are highlighted.
