Plausible mechanisms 9-11 that could reduce the number of driver gene mutations in obesity include (a) obesity-induced survival and proliferative signaling pathways (e.g., ERK and AKT) that substitute for driver gene mutations activating the same pathways in normal-weight patients, (b) obesity-induced changes in the gut microbiome 10 and its downstream pathways that substitute for driver gene mutations, (c) obesity-induced epigenetic changes that substitute for driver gene mutations, and (d) stem cell numbers that are increased in obesity [11 and refs. therein]. This evidence concerns the gene AKT1 and obesity due to melanocortin 4 receptor deficiency.