Inactivation of both TP53 and RB1, occurring either by genomic alterations or protein downregulation,2,6,8 is an early biomarker of high risk of NE transformation.6,8 Interestingly, inactivation of either of these tumor suppressor genes separately has been associated with increased CDC7 expression in tumor types including LUAD.15,23 Analysis of publicly available transcriptomic datasets of clinical adenocarcinoma specimens showed increased expression of CDC7 mRNA in LUAD and PRAD with concurrent TP53 and RB1 mutations relative to double wild type (wt) tumors (Fig. 2a). Here, RB1 is linked to neoplasm.