Abstract
Hereditary diffuse gastric cancer (HDGC) is an inherited form of diffuse type gastric cancer. Germline CDH1 mutations have been identified in approximately 15-50 % of affected kindred that meet the clinical criteria for HDGC. If any of the criteria is met the individual is referred to genetic counseling and CDH1 testing is offered. In this report we present the case of a Spanish family with HDGC harboring a novel CDH1 mutation. A 47 year-old female with a diagnostic of gastric adenocarcinoma and some of her relatives were tested. Study of the entire CDH1 gene, including intron-exon boundaries, by PCR and sequencing and immunohistochemical determination of the expression of E-cadherin were performed. A novel heterozygous deletion in exon 9 of CDH1 gene (c.1220_1220delC, p.P407Qfs10), was found in the proband, one sister and a nephew. It generates a premature stop codon giving rise to a truncated protein that leads to a pathogenic variant. Expression of E-cadherin was absent or frankly reduced in the proband's tumor but normal in tumor cells of great-uncle. After these results, the sister underwent prophylactic total gastrectomy, and the nephew is under annual endoscopic surveillance. Personal or familial history of diffuse gastric cancer, above all at young age, should encourage CDH1 genetic testing. In this sense, the review of the criteria and the addition in the last guideline of the recommendation: "other families in which genetic testing may also be considered" broadens the number of individuals at risk detected. Since there are not reliable methods for early detection, DGC is usually diagnosed at an advanced stage and consequently associated with a poorer outcome. Thus, CDH1 mutations detection contributes to an improvement in diagnosis and therapeutic intervention.