Fig. 1
From: Correlation of an epigenetic mitotic clock with cancer risk
Flowchart of epiTOC. a The epiTOC score (also pcgtAge score) is estimated over 385 PCGT/PRC2-marked promoter CpGs that are constitutively unmethylated in over 37 fetal tissue samples from 12 tissue types and whose DNAm increases with chronological age in a large cohort of healthy individuals, as assessed in one tissue type (blood). The epiTOC/pcgtAge score of any sample represents the average DNAm from the ground fetal state over these 385 sites, representing the life-time accumulation of DNAm replication errors, and provides a relative estimate of the number of stem cell divisions per stem cell. The lower panel shows how this score varies linearly with chronological age (data as estimated in the Hannum et al. [28] blood dataset). b Validation of the epiTOC/pcgtAge score by correlation to the estimated intrinsic rate of stem cell division per stem cell in normal tissue samples from The Cancer Genome Atlas (TCGA) for which such estimates are available. Further validation of epiTOC/pcgtAge by correlation to an mRNA expression-based mitotic index in cancer tissues from TCGA. c Assessment of whether epiTOC/pcgtAge is accelerated in precancerous lesions (lung carcinoma in situ (LCIS) and ductal carcinoma in situ of the breast (DCIS) and cancer (TCGA) and whether it can predict the prospective risk of invasive lung cancer (ILC)