Clinical approach for managing patients with unexpected CDH1 mutations: A case report

Abstract

AbstractBackgroundHereditary diffuse gastric cancer (HDGC) (OMIM# 137215) is an autosomal dominant cancer syndrome associated with CDH1 (OMIM# 192090) mutations. Prophylactic total gastrectomy (PTG) is the most recommended preventive treatment when a pathogenic mutation is found. However, the increasing use of genetic testing has led to the identification of incidental CDH1 mutations in individuals without a family history of gastric cancer. It remains unclear whether these patients should undergo prophylactic total gastrectomy.MethodsGermline DNA, obtained from peripheral blood, was analysed by NGS.ResultsA 47‐year‐old woman was diagnosed with high‐grade serous ovarian carcinoma, FIGO stage IIIC, with a Homologous Recombination Deficiency (HRD) GIS status of 78 (positive, cut‐off: 43). She received chemotherapy and niraparib treatment. A multigene panel test revealed no pathogenic mutations in BRCA1 (OMIM# 113705)/BRCA2 (OMIM# 600185) genes, but a de novo deletion of exon 16 in CDH1 was found incidentally. She had no previous family history of gastric or breast cancer. The patient was enrolled in a surveillance program involving periodic endoscopy and was diagnosed with diffuse gastric cancer through biopsies of a pale area in the antrum after 1 year of close endoscopic follow‐up.ConclusionThis case presents supportive evidence for the pathogenic classification of the loss of the last exon of CDH1.