Of note, alterations in tumor suppressor genes, particularly TP53, p16/CDKN2A, SMAD4, and TGFBR2, as well as mutations of mTOR pathway genes (PTEN, PIK3CA, and AKT1) are associated with advanced neoplasia (high-grade dysplasia and invasion) [23,24,25,26,27,28,29]. Here, SMAD4 is linked to neoplasm.