Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) are complex diseases with undiscovered genetic factors. We successfully discovered a deleterious variant in VSIG10L segregating in a large family. This is the first such reported gene for susceptibility to BE and EAC. VSIG10L appears to function in adhesion and differentiation/maturation of stratified squamous epithelium. The BETRNet focus of Project 1 is thus to create a genetically engineered mouse model based on VSIG10L to understand the transformation from squamous epithelium to metaplastic Barrett’s epithelium.
- Using genetically engineered VSIG10L knockout and VSIG10L S631G variant carrying mice we will understand how VSIG10L contributes to the normal squamous epithelium esophagitis BE metaplasia dysplasia cancer progression.
The significance of Project 1 is clearly in building on our successful discovery of the first familial susceptibility genetic variant by understanding how this gene functions in metaplastic transformation of Barrett’s epithelium.