In our cohort, the promoter region of the HES5 gene showed the largest and most consistent increase in methylation in tumour samples compared with matched normal tissue (median 7.6-fold increase, median variance=0.003), together with consistently low methylation in adjacent normal tissue (median normal methylation=0.08, median variance=0.0006; Fig. 1b, c, d and Supplementary Figure 1f, g, h, i, j, k, l, m). The gene discussed is HES5; the disease is neoplasm.