Combination of these analyses with CNA/LOH analysis indicate that alteration of NOTCH1 and NOTCH2 genes are among the most common events in cSCC (Fig. 3) with only 3/20 MD/PD tumours and 5/20 WD tumours escaping alteration in either of these genes indicating that the NOTCH pathway is an almost universal tumour suppressor pathway in cSCC probably due to its role in promoting cell cycle exit and differentiation57. Here, NOTCH2 is linked to Wilson disease.