Fig. 4: Spatial phylogenomics of colorectal cancer.

a, In this MSI tumour (C516) the cancer (regions A and B) and macroscopically diagnosed advanced adenoma (regions C and D) formed a large mass and were physically adjacent to one another. Photo indicates sampling quadrant, not precise location. b, The advanced adenoma shared multiple drivers with the cancer but showed early divergence. c, Tumour C551 presented with a cancer and a concomitant adenoma that were very distant, indicating two independent events. d, The phylogenetic tree was characterized by clonal intermixing of diverging lineages collocated in the same region (for example, some lineages from regions A, B and C were genetically close). Subclonal drivers of unknown significance were present, including a non-expressed variant in USP6 and an ARID1A mutation. Early divergence between the cancer and adenoma F was evident, with no shared drivers between the two lesions. e, Tumour C561 presented with a large cancer mass and multiple small concomitant adenomas. f, Again, there was no notable somatic alteration in common between the different lesions. The cancer showed clonal amplification of MYC and only a benign subclonal mutation in FAT4. g, Phylogenetic reconstruction of four further tumours with annotated driver events. h,i, Phylogenetic trees with matched in situ mutation detection with BaseScope for the KRAS G12C subclonal variant in C539 (h) and the PIK3CA E545K subclonal variant in C537 (i). Staining by haematoxylin and eosin (H&E) and BaseScope were each performed once; scale bars, 50 μm.