The activity of many metabolic pathways that distinguish SCC from AdC tumours, including glycolysis, PPP, the Krebs cycle and nucleotide biosynthesis, are required to support higher proliferation, as previously reported for SCC compared with AdC tumours.39,53,54 It is also consistent with both NOTCH1 and MYC being master regulators of cell proliferation.47,55 At the same time other differences, like higher reductive carboxylation of glutamine, may reflect differences in other cell autonomous functions or the tumour microenvironment. The gene discussed is NOTCH1; the disease is AIDS dementia complex.