CDH1 germ-line missense mutation identified by multigene sequencing in a family with no history of diffuse gastric cancer

• The patient was referred to a Genetic Counseling service for presenting familial history.
• Multigene sequencing of 94 genes that predispose to several cancers was performed.
• CDH1 missense mutation A617T in heterozygous and 4 BRCA2 SNPs in homozygosis was found.
• CDH1 A617T mutation is not related to HDGC nor ILC in this family.
• This is the first report of a family with CDH1 A617T mutation and no HDGC.

Germ-line mutation in CDH1 gene is associated with high risk for Hereditary Diffuse Gastric Cancer (HDGC) and Infiltrative Lobular Carcinoma (ILC). Although somatic CDH1 mutations were also detected in ILC with a frequency ranging from 10 to 56%, CDH1 alterations in more frequent infiltrative ductal carcinoma (IDC) appear to be rare, and no association with germ-line CDH1 mutation and IDC has been established. Here we report the case of a woman diagnosed with IDC at 39 years of age, presenting extensive familial history of cancer at multiple sites with early-age onset and with no case of HDGC. Deep sequencing have revealed CDH1 missense mutation c.1849G>A (p.Ala617Thr) in heterozygous and four BRCA2 single nucleotide polymorphism in homozygosis. In this family, the mutation c.1849G>A in the CDH1 gene is not related to HDGC nor ILC. Therefore, here we highlight that multigene analysis is important to detect germ-line mutations and genetic variants in patients with cancers at multiple sites in the family, even if inconclusive genetic counseling can be offered, since hereafter, medical awareness will be held.