Gastric and oesophageal tumours are, jointly, the second most common cause of cancer death globally. The poor survival (approx. 15% 5-year survival) of patients diagnosed with these tumour types stems from the frequent late diagnosis. However, the early diagnosis of these tumours dramatically increases patients’ 5-year survival to over 75%. Our ability to detect early stages of gastric and oesophageal cancers is limited by our understanding of how these cancers develop. For decades, we have known that these cancers develop via precancerous lesions called Barrett’s Oesophagus and Gastric Intestinal Metaplasia. However, despite decades of clinical knowledge our molecular understanding of precancerous lesion and their relationship with cancer and, importantly, normal tissues they originate from is limited. The Tumorigenesis and Molecular Cancer Prevention Research Group uses state-of-art approaches to characterize and model early transcriptional, genetic and epigenetic processes that drive the development of gastro-oesophageal tumours and their precancerous lesions. A critical part of our work is to understanding how normal cells of the stomach and oesophagus lose their molecular identity and slowly transform into (pre)cancerous states. Using single-cell RNA sequencing, we demonstrated that, despite its name, Oesophageal Adenocarcinoma, a subtype of Oesophageal Cancer, originates from the stomach. It is also molecularly indistinguishable from other gastric cancers. Our work has also shown that the precancerous lesions have unique molecular properties that can only be described as single-cell molecular mosaicism – a state in which cells can stably maintain a mixed phenotype that is normally observed in two different cell types of the human body.
