Submitted by Dr Hayley B. Wo... on Fri, 10/09/2021 - 13:11
Discovery of origin of oesophageal cancer cells highlights importance of screening for pre-cancerous Barrett’s oesophagus.
A multidisciplinary group of scientists led by Professor Rebecca Fitzgerald (Department of Oncology, CRUK Cambridge Centre Early Detection Programme Lead), has recently published their findings regarding the origin of oesophageal cancer cells - see Nowicki-Osuch, K & Zhuang, L et al. Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition(link is external). Science; 13 Aug 2021.
The team found that a particular subtype of oesophageal cancer known as oesophageal adenocarcinoma is always preceded by Barrett’s oesophagus – abnormal cells of the oesophagus – even if these cells are no longer visible at the time of cancer diagnosis. This confirms that screening for Barrett’s is an important approach to oesophageal cancer control.
Cancer of the oesophagus is the sixth most deadly cancer, and oesophageal adenocarcinoma is on the rise in western countries.
It has been known for some time that the development of this cancer is linked with Barrett’s oesophagus, and affects around one in every 100 to 200 people in the United Kingdom, with between 3 and 13 people in 100 with this condition going on to develop oesophageal adenocarcinoma in their lifetime. However, the question of where these abnormal cells come from was still a mystery.
The research team analysed tissue samples from patients with Barrett’s oesophagus and from organ donors who have never had the condition to generate a detailed ‘atlas’ of human cells and tissues from all possible origins of Barrett’s oesophagus. They then compared the maps of cells from healthy tissues, Barrett’s oesophagus and oesophageal adenocarcinoma using a number of state-of-the-art molecular to trace the origins of particular cell types.
Their results showed a striking similarity between stomach cells and Barrett’s oesophagus, suggesting that the cells at the very top of the stomach can be reprogrammed to adopt a new tissue identity, becoming more like intestine cells, and replace the oesophageal cells. Furthermore, in this new study the team showed that two genes, MYC and HNF4A, are the keys that switch the tissue identity from stomach to intestinal cells.
Importantly, the researchers found that all oesophageal adenocarcinoma cells begin as stomach cells before transforming into Barrett’s cells and then into cancer cells and revealed the internal processes that cause this transition, but what triggers these genes is still unknown.
It is anticipated that these insights into the origin of oesophageal adenocarcinoma could help inform future research efforts into how to diagnose this type of cancer early, which is key for improving patient outcomes.
The research was largely funded by the Medical Research Council, Wellcome and Cancer Research UK.