Extended Data Fig. 2: Recurrent copy number aberrations in TP53-deficient gastric organoids are enriched in gastric and esophageal cancers.
From: Deterministic evolution and stringent selection during preneoplasia
a, Prevalence of somatic alterations and fraction genome altered in gastric cancer (stomach adenocarcinoma, STAD) from TCGA in all subgroups versus the CIN subgroup. Data derive from the cBioPortal. b, Frequency of chromosome arm alterations in TP53−/− HGOs (ORG) at late time points (days 588 to 835, as in Fig. 1c) relative to other tumour types: Stomach Adenocarcinoma (STAD), Esophageal carcinoma (ESCA), Colorectal Adenocarcinoma (COAD), Rectum Adenocarcinoma (READ), Breast invasive carcinoma (BRCA), Glioblastoma Multiforme (GBM), Pancreatic Adenocarcinoma (PAAD). TCGA data were obtained from Firehose (http://gdac.broadinstitute.org/#). c, Enrichment of chromosome arm-level alterations in TP53−/− gastric organoid cultures across cancer types. Boxes show inter-quartile range (IQR), center lines represent the median, whiskers extend by 1.5 × IQR. Arm-level CNAs altered in two or more TP53−/− gastric organoid cultures (n = 12 alterations) were more frequently altered than alterations present in 1 or fewer cultures (n = 66 alterations) in both STAD and ESCA (p-value shown, two-sided Wilcoxon rank sum test). d, The Jaccard Index (JI) was calculated by comparing CNAs that occurred in more than 1 chromosome arm in organoid cultures with CNAs occurring in 15% or more cases in a given tumour type. Permutation tests were performed to determine if the JI score was higher than expected by chance (i.e. one-sided test). For each tumour type, organoid CNA labels were randomly sampled (n = 10,000) from all possible chromosome arm-level events, and the JI was calculated. The empirical p-value was calculated as: P = 1-(sum(real JI > null JIs)/number of null JIs). Boxplot represents median, 0.25 and 0.75 quantiles with whiskers at 1.5 × IQR and includes the nominal p-values. e, Oncoplot shows alterations that occurred in two or more samples for genes commonly (>10% of cases) altered in gastro-esophageal cancer.
