Transcriptomic profiling of signet ring cell precursors of diffuse-type gastric cancer informs latent phenotype

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 single cell RNA sequencing (scRNA-Seq) of normal-appearing gastric mucosa that contained SRC lesions from three patients that contributed a total of 20 replicates (eight replicates each from patients 1 and 2, and four replicates from patient 3).