SMAD4 and cancer: Recurrent mutations in TP53 have been observed in high-grade dysplastic Barrett’s esophagus and esophageal adenocarcinoma, however SMAD4 mutations have only been observed in invasive lesions.32 The differential profiles of cancer through tumorigenesis starting at early lesions to advanced/invasive disease may provide a unique avenue for early detection, particularly if we can pinpoint specifically which early events leads to cancer progression.