LAUSR

Simple Summary Diffuse gastric cancer is the hallmark of the hereditary diffuse gastric cancer syndrome related with the E-cadherin germline mutations. Other cancers (non-gastric) are described in association with the CDH1 gene germline alterations. In this study, we aimed to assess the overall frequency of CDH1 mutations in non-gastric tumors reported in literature so far. Abstract Hereditary Diffuse Gastric Cancer (HDGC) is a complex inherited syndrome caused by CDH1 germline mutations. DGC is the hallmark cancer of this genetic predisposition, but several other cancers are associated with these CDH1 mutations. In this review, we revised all studies reporting CDH1 mutations in non-GC patients. The selected studies included: (a) families aggregating with GC and other cancers, both, and (b) families presenting only non-gastric tumors association. Among non-gastric tumors, our results show that CDH1 mutations are most frequently identified in breast cancer. The frequency of missense mutations is higher in the non-GC group, as the age at diagnosis in this group. Moreover, the predominant CDH1 mutation affects the extracellular domain. Our data suggest that CDH1 genetic testing should be considered also in other cancers, especially breast tumors.