CDC6 is a necessary component of the pre-replication complex at origins of replication and involved in cell-cycle progression-control via a mitotic checkpoint.47 It mediates oncogenic activity through repression of the INK4/ARF tumor suppressor pathway48 and is an activator of oncogenic senescence.49 In breast cancer, its expression correlates with poor prognosis.50PTPRK is among the few CTCF TFBS single-hit genes with unexpected expression correlation, with a single mutation in liver cancer (Fig. 5h, j). Here, CDKN2A is linked to breast cancer.