We identified a somatic CpG hypermutator phenotype in 1.1% (19/1661) of tumours (Fig. 5A; Table EV5), and a strong enrichment of mutations in the MutSα complex genes (MSH2/MSH6) in tumours with a somatic CpG hypermutation phenotype (53%) relative to tumours with a high (12%, OR = 8.5, P = 2.7e–5) and low TMB (0.9%, OR = 113, P = 2e–14) (Fig. 5B). Here, MSH2 is linked to neoplasm.