Although inhibitors of purine biosynthesis are predicted to be synthetically lethal in cancers with defects in MTAP, at least in vitro, this effect may be bypassed if tumour cells take up adenine from the microenvironment.114 Loss of MTAP also results in accumulation of its substrate MTA, which inhibits protein arginine methyltransferase 5 (PRMT5), a key enzyme that methylates arginine side chains of proteins including histones, thus affecting chromatin remodelling and epigenetic control of gene expression (Fig. 4). Here, MTAP is linked to cancer.