Identification of a primitive intestinal transcription factor network shared between esophageal adenocarcinoma and its pre-cancerous precursor state

Oesophageal adenocarcinoma (OAC) is one of the most frequent causes of cancer deaths and yet compared to other common cancers, we know relatively little about the molecular composition of this tumour type. To further our understanding of this cancer we have used open chromatin profiling to decipher the transcriptional regulatory networks that are operational in OAC. We have uncovered a transcription factor network that is usually found in primitive intestinal tissue during embryonic development, centred on HNF4A and GATA6. These transcription factors work together to control the OAC transcriptome. Importantly, we show that this network is also activated in Barrett9s oesophagus, a precursor state to OAC thereby providing molecular evidence that further links Barrett9s oesophagus to OAC. Furthermore, we show that HNF4A alone, is sufficient to drive chromatin opening and activation of a Barrett9s-like chromatin signature when expressed in normal epithelial cells, indicating that HNF4A activation might be a pivotal event in generating this pre-cancerous state.