FIGURE 1: Early events underlying carcinogenesis. (A) Cancer arising from normal cells subject to a somatic driver mutation as the initial event, with subsequent alterations leading to malignant transformation. In such cases the initial event will not be detected in white blood cells (WBC). (B) Cancer arising from normal cells harbouring a germline driver mutation, acting as the initial event, with subsequent alterations leading to malignant transformation. In such cases the “initial event” will be detectable in all WBCs. (C) Cancer arising from a minority of normal cells with a key tumour suppressor methylated from early embryonic life (epigenetic mosaicism). This methylation may act as the initial event, with subsequent alterations leading to malignant transformation. In such cases the initial event/methylation will be detectable also as mosaicism in WBC.