Mutations present in nearly all tumour cells (clonal) would suggest early events and therefore represent initiating ‘driver' genes as appears to be the case here for NOTCH1, NOTCH2, CDKN2A, HRAS, KRAS, TP53 and, importantly, both TGFBR1 and TGBFR2. This evidence concerns the gene NOTCH1 and neoplasm.