Fig. 1: Brca2 depletion in Villin-positive cells promotes gastrointestinal cancer formation by increasing genome instability.

a Mutation status of FA- and FA-like members in 2014 TCGA stomach adenocarcinoma samples (n = 293). MSI, high microsatellite instability; GS, genomic stable; EBV, Epstein-Barr virus positivity; CIN, chromosomal instability. b Survival curves of BRCA2-low (n = 209) and BRCA2-high (n = 145) mRNA expression cases from provisional TCGA gastric cancer databases. *p < 0.05. c Brca2 staining in the stomach tissues of Brca2 wild-type and knockout mice. Scale bar, 10 μm. d Experimental design: Three-week-old Brca2 knockout mice or littermate wild-type mice were divided into four groups; MNU was administered to mice in two groups via drinking water at 120 mg/L on alternate weeks for a total exposure of 10 weeks, and vehicle was administered to the other two groups. e Disease incidence of Villin-Cre⁻; Brca2^fl/fl mice (n = 10, WT group), Villin-Cre⁺; Brca2^fl/fl (n = 12, KO group), Villn-Cre⁻; Brca2^fl/fl with MNU (n = 16, WT plus MNU group), and Villin-Cre⁺; Brca2^fl/fl with MNU (n = 18, KO plus MNU group). f Tumor incidence and location of all the tested mice in the four groups. g Kaplan–Meier survival curves of Brca2 wild-type (n = 10) and knockout mice (n = 12) without MNU treatment. h Kaplan–Meler survival curves of Brca2 wild-type (n = 8) and knockout mice (n = 6) with MNU treatment. **p < 0.01. i Gross morphology and H&E staining of stomach sections from 10-month-old MNU-treated Brca2 wild-type and knockout mice. The white arrow indicates the visible tumors of Brca2 knockout mice. Scale bar, 200 μm. j Disease incidence and location of Villin-Cre⁺; Brca2^+/+; Trp53^fl/+ mice (Group A, n = 5) and Villin-Cre⁺; Brca2^fl/fl; Trp53^fl/+ mice (Group B, n = 9). k Kaplan–Meier survival curves of Villin-Cre⁺; Brca2^+/+; Trp53^fl/+ and Villin-Cre⁺; Brca2^fl/fl; Trp53^fl/+ mice. *p < 0.05.