Spatial transcriptomic profiling of signet ring cell precursors of diffuse-type gastric cancer

Germline CDH1 loss-of-function mutations are causally linked to an increased lifetime risk of diffuse gastric cancer (DGC). Early, multifocal signet ring cell (SRC) lesions are ubiquitous among CDH1 variant carriers, yet only a subset of patients will develop advanced DGC. Transcriptomic profiling was performed to establish the molecular phenotype of early SRC lesions. Overall design: We performed NanoString GeoMx digital spatial profiling (DSP) using the whole transcriptome atlas (WTA) panel to characterize gastric tissue regions of interest (ROIs). Early tumor stage (T1a) gastric epithelial (T1a_NEP) and SRC lesion (T1a_SRC) ROIs were captured from total gastrectomy samples of four patients with germline CDH1 P/LP variants. In four patients with advanced DGC found on gastrectomy explants, ROIs were selected from gastric epithelial (GC_NEP), superficial lamina propria (GC_sup), as well as from submucosa and deeper (GC_deep).