This was consistent with the finding that high-grade CS tumors are characterized by the up-regulated expression of NAD+ biosynthesis genes such as nicotinate phosphoribosyltransferase (NAPRT), nicotinamide phosphoribosyltransferase (NAMPT), and indoleamine2,3-dioxygenases (IDO). This evidence concerns the gene NAPRT and Cowden syndrome 1.