When we were studying the interaction between the neoplastic cells and stromal fibroblasts in the PDAs, we found that neoplastic cells can induce DNA methylation at a whole-genome level in CAFs.5 Prior to our study, Shakya et al. had compared the gene expression profiling between DNA-demethylating agent-treated CAFs and untreated CAFs from the PDA tumors of a genetically engineered mouse model of PDA, the KPC-Brca1 mouse model,19 and found that Aldh1a3 in the glucose metabolism pathway and Nqo-1 in the OXPHOS pathway was regulated by DNA methylation. The gene discussed is ALDH1A3; the disease is Patent ductus arteriosus.