Modelling hereditary diffuse gastric cancer initiation using transgenic mouse-derived gastric organoids and single-cell sequencing

Hereditary diffuse gastric cancer (HDGC) is a high-penetrance cancer syndrome caused by germline variants in CDH1, a tumour suppressor gene encoding the cell-cell adhesion molecule E-cadherin. Loss of E-cadherin in gastric and other cancers is associated with cellular dedifferentiation and poor prognosis. However, the mechanism through which CDH1 loss initiates HDGC is not known. Here we explored the single-cell transcriptome of organoids derived from transgenic mice to better understand the impact of CDH1 loss in the early pathogenesis of HDGC.