Mutations were classified as clonal if the cancer cell fraction was >0.95 with a probability >0.5 and subclonal otherwise.30 In additional cases with proven-somatic SETD2 mutations (n=4) and paired copy-number data from our pre-treatment validation cohorts, we performed this estimation by manually correcting for tumour sample purity and local copy number. Here, SETD2 is linked to cancer.