Molecular characterization of Barrett’s esophagus at single-cell resolution

Significance Barrett’s esophagus (BE), the premalignant condition of esophageal adenocarcinoma, is categorized into different stages which correlate with the risk of developing carcinoma. We performed single-cell DNA-sequencing experiments with fresh biopsies, which revealed the appearance of a specific T > C and T > G mutational signature, known as COSMIC signature SBS17, in BE cells that are chromosomally unstable. The SBS17-specific mutations were, however, not detected in chromosomally stable BE cells. Additionally, we performed single-cell RNA sequencing experiments which identified seven genes that facilitate the distinction between different BE stages on histological sections.