TP53 and neoplasm: To model tumour initiation in CIN GC, we established HGOs from non-malignant tissue from three human donors undergoing gastrectomy and introduced biallelic TP53 frameshift mutations via CRISPR–Cas9, resulting in an inactive gene product (Fig. 1a, Extended Data Fig. 1, Supplementary Figs. 1–3, Supplementary Tables 1 and 2 and Methods).