SETD2 and cancer: Our pan-cancer analyses showed that LF1 signature was associated with the patient’s chronological age (P = 8.1 × 10−40), epiTOC2 (P < 1.0 × 10−307), dosage of the clock-like mutational signature SBS1 (P = 2.8 × 10−15), WGS-telomere length ratio (P = 0.022), copy number alterations (P = 1.0 × 10−05), and the presence of PBRM1 (P = 1.3 × 10−10) and SETD2 (P = 2.2 × 10−09) somatic cancer driver genes, independent to ccRCC tumours (TCGA-KIRC) (Table 2).