NOTCH1 and esophageal squamous cell carcinoma: Although the origin of ESCC has previously been associated with field cancerization involving both epigenetic and genetic defects that give rise to multifocal dysplasia in esophageal and other tissues [32, 33], the clinical evidence is scant and may be confounded with the ubiquitous presence of driver mutations (TP53, Notch1) in normal squamous tissue [34].