Fig. 1: Somatic mutation analysis of 1,063 CRC genomes identifies 96 driver genes.

Somatic mutations were called (Methods) and significantly mutated genes were identified using dNdScv. a, The 96 genes mutated at a significant level in this cohort. The association of driver genes with survival (HR) is shown for HM and nHM tumours (multivariable Cox regression). The association of driver genes with clinical and genomic features is shown by the proportion of tumours affected (Fisher’s exact test). *FDR-adjusted P < 0.05. The mutation type and prevalence is indicated on the right, including a description of the affected pathway. Colour keys for HR for OS and RFS, and for genomic feature proportions are shown on the far right. Genes that were not previously designated as drivers in CRC (orange) or in any cancer type (blue) are indicated. b, The prevalence of total (blue) and non-synonymous (red) mutations in each tumour. Cut-offs for HM and nHM are indicated (grey line). The clinical features and mutation status for selected genes are shown at the bottom. Mutations that are considered to be drivers are either probably oncogenic mutations annotated by OncoKB or hotspots catalogued by Cancer Hotspots. c, DNA damage response (DDR) gene mutations in the 15 out of 21 HM tumour cases that were MSS. Not all DNA damage response genes included here can be interpreted as the direct cause of the high TMB in these MSS samples. Top, the total non-synonymous mutation counts for each sample are coloured by the affected oncogenic pathways. ADENOCA, adenocarcinoma; BER, base excision repair; HRR, homologous recombination repair; MMR, mismatch repair.