NE relative to non-NE tumors exhibited marked upregulation of genes essential for cancer cells to cope with the increased rates of replication (TOP2A, MCM3), and prevent replication stress-induced DNA damage, including those related to the DNA damage response (CHEK1, -2, TP53BP1, TOPBP1), cell cycle progression (CDC25A, -B, -C, CDK1, -2, AURKA, -B, CDK1, -2, PLK1, CCNB1, -2, CCNA2), and DNA repair (PARP1, -2, BRCA1, RAD51, PRKDC) (Fig. 4a, S11d). This evidence concerns the gene PRKDC and cancer.