Fig. 1: TP53 deficiency in HGOs induces aneuploidy and GC-associated CNAs along a defined temporal order.
From: Deterministic evolution and stringent selection during preneoplasia
a, Schematic overview of HGO establishment and generation of TP53–/–, TP53–/– and APC–/– cultures via CRISPR–Cas9 editing (Methods). b, Genome-wide CNA profiles of D1C1 at multiple time points assessed by sWGS. Normalized read counts across 50 kb genomic windows for each time point. c, CNA profiles for the nine organoid cultures sampled between days 588 and 835. d, FGA over time for each culture. e, Time of appearance (days in culture) of persistent arm-level CNAs (or alterations in FHIT and CDKN2A) in TP53/APC-deficient organoids (alterations that became extinct were not considered). The prevalence of these alterations in GC is summarized in Extended Data Fig. 2a,b. Boxes show interquartile range (IQR), centre lines represent the median and whiskers extend by 1.5× IQR. Sample size per aberration (n): 3p– (4), 9p– (7), FHIT (7), 4q– (2), 3q+ (3), 4p– (3), 14q+ (2), CDKN2A (2), 18q– (6), 15q– (2), 20q+ (5), 18p– (2), 11q+ (3), 11p+ (2). KO, knockout. Image of stomach in a is from Servier Medical Art, CC BY 3.0.
