PROJECT SUMMARY/ABSTRACT The incidence of esophageal adenocarcinoma (EAC) has increased more than 6-fold in the past three decades while the prognosis has remained poor. Barrett's esophagus (BE) is the only known precursor of EAC. Endoscopy (EGD) is the current method to diagnose BE but because EGD is expensive and screening is not recommended very few EACs are detected in patients with pre-diagnosed BE. To make an impact on the prevention and early detection of EAC the challenge is to first develop an alternative method for identifying BE that is less costly and safer than EGD while being acceptable and accessible. The second step is to discover biomarkers that can effectively identify high grade dysplasia and early cancer. We have demonstrated that methylated Vimentin and other methylated biomarkers can detect BE in esophageal brushings. In addition, we have developed a panel of biomarkers (TP53 mutations, 4 methylated markers, and 2 linc-RNA markers) that sensitively and specifically identify EAC. Furthermore, the linc-RNAs in our marker panel also play a role in BE carcinogenesis. Thus, our aim is to – 1) diagnose BE using methylated Vimentin (plus other biomarkers) testing with a novel esophageal sampling device; 2) validate our marker panel for detecting high grade dysplasia and cancer; and 3) determine the mechanism by which linc-RNAs promote the progression of BE to EAC. The results of this study will lead to an early detection strategy for EAC and improve our understanding of esophageal carcinogenesis.