Fig. 1: Intratumour heterogeneity of somatic mutations.

a Tumour size, location, TNM-stage and regions selected for sequencing. The grey line labelled (Z) marks the gastro-oesophageal junction. b Immunohistochemical staining of MLH1, MSH2, MSH6 and PMS2. c Heat maps showing the presence (blue) or absence (grey) of non-silent somatic mutations that were identified by MSeq across tumour regions. The table shows the number of heterogeneous (Het) and ubiquitous (Ub) mutations identified in each tumour and their percentage of the total non-silent mutation count of the tumour. d Comparison of ubiquitous and heterogeneous mutation counts across four different tumour types analysed by MSeq (dMMR GOA: mismatch repair deficient gastro-oesophageal adenocarcinoma, Melanoma, NSCLC: non-small cell lung cancer, ccRCC: clear cell renal cell carcinoma). The Mann–Whitney test was used to assess significant differences in mutation loads between dMMR GOA and other tumour types. e Median mutation loads of individual regions from MSeq datasets compared to the median single sample mutation loads from the Cancer Genome Atlas KIRC, SKCM, STAD and LUAD cohorts. f COSMIC mutational signature analysis of ubiquitous (Ub) and heterogeneous (Het) mutations in four dMMR GOAs. Non-silent and synonymous mutations were included in the analysis and only signatures which contributed to ≥5% of mutations in at least one sample are shown.