Diffuse gastric cancer: histologic, molecular, and genetic basis of disease

Diffuse gastric cancer (DGC) is a distinct histopathologic and molecular disease, characterized by mutations in CDH1, RHOA, and others. In addition, DGC is associated with familial syndromes, including hereditary DGC and germline mutation in CDH1. Clinically, this subtype of gastric adenocarcinoma is associated with a poor prognosis and possible resistance to available systemic therapies. An understanding of the genetic and molecular underpinnings of DGC may help inform of its clinical behavior and aid in screening, diagnosis, and response to treatment. In this review, we will review the current histologic, molecular, and genetic landscape of DGC and its relevance to clinical practice.