Extended Data Fig. 3: Clonality and positive selection of SMGs in gastric cancer.

Landscape of SMG clonality and positive selection in (a) non-hypermutated and (b) hypermutated cases. The median of the adjusted variant allele frequencies (aVAFs) of each SMG indicates clonality on the horizontal axis. The q value (-log10 q value) indicates the degree of positive selection on the vertical axis. Genes with activating and inactivating mutations are indicated in red and blue, respectively. (c) Distribution of aVAF of the B2M gene in non-hypermutated and hypermutated cases. High (>0.4) B2M aVAF was more frequent in hypermutated cases. (d) Degree of positive selection (denoted by q value of SMG tests) of 29 non-long-tail SMGs (altered in ≥3% of cases) and 39 long-tail SMGs (altered in <3% of cases) in non-hypermutated cases. The types of alterations and q-values are shown. The solid black line indicates the cutoff (altered in 3% of cases) between non-long and long-tail SMGs. (e) Molecular pathological features of RB1-mutated cases. A fraction of RB1-mutated cases showed higher expression of neuroendocrine markers (ASCL1, CHGA, NCAM, and SYP) (left). Boxplots represent the median and 25th and 75th percentiles of the data. Whiskers represent the highest and lowest values within 1.5 times the interquartile range of the boxplot. Histologically, RB1-mutated cases with high neuroendocrine marker expression showed densely packed cells with a high nuclear-cytoplasmic ratio as high-grade neuroendocrine features (right). The scale bar indicates 250 µm.