Clone 4 descended from clone 3 after acquiring an additional 239 mutations in cluster d. This cluster included a somatic splice site mutation of PMS2, which encodes post-meiotic segregation increased 2, a protein involved in mismatch repair that is mutated in hereditary non-polyposis colorectal cancer (Lynch syndrome) and other tumours15. Here, PMS2 is linked to hereditary nonpolyposis colon cancer.