Mechanisms underpinning the progression of nondysplastic Barrett's oesophagus to cancer.

Barrett's oesophagus is the metaplastic precursor to oesophageal adenocarcinoma; it is initiated by exposure of the squamous oesophageal epithelium to acid reflux. Wound repair mechanisms lead to the migration of columnar cells into the denuded lower oesophageal niche. These columnar cells remain exposed to inflammatory acid and bile reflux, which serves as a mutagenic pressure and induces the appearance of intestinal phenotypic features. The patchwork accumulation of genomic instability after TP53 loss provides a cancerised field where dysplastic clones can be selected for. In our review, we demonstrate that this likely needs to occur in concert with a permissive microenvironment with altered immune and stromal interactions underpinning this. Accurately measuring this risk is difficult as the Barrett's lesion is both genomically and phenotypically diverse and a single biopsy sample may miss the divergent evolutionary trajectories of individual Barrett's clones. However, new technologies may overturn this and eventually allow for improved clinical risk prediction, which will have important implications for cancer detection and treatment.