Hereditary diffuse gastric cancer in two families: A case report

Abstract

Abstract. Hereditary diffuse gastric cancer (HDGC) is associated with E-cadherin 1 (CDH1) germline mutations. In the present study, two unusual HDGC cases are described. Case 1 was a female with no family history of gastric cancer who developed Hodgkin's lymphoma at 19 years of age, and DGC at 32 years of age. Due to her young age (32 years), the patient was examined for CDH1 abnormalities and a deleterious mutation was identified. Her father and younger sister were identified to be carriers of the mutation. Case 2 was a 36-year-old female diagnosed with lobular breast cancer (LBC); her mother had LBC, and her grandmother had LBC and DGC. The molecular test was wild-type for breast cancer susceptibility genes 1 and 2; however, a large deletion in CDH1 was identified. At prophylactic gastrectomy, early DGC was identified. Early onset of DGC and LBC justifies testing for CDH1. A better knowledge of tumor natural history in carrier subjects is important to aid genetic counseling, in order to assess the surveillance time required prior to carrying out prophylactic surgery.

Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity

“…In 1998, Guilford et al found multiple cases of early-onset DGC in Maori ethnic peoples of New Zealand that were carriers of a three germline truncating mutation in the E-cadherin ( CDH1 ) gene [23]. Several other publications emerged confirming the association of autosomal-dominant pattern of inheritance with germline mutations of the CDH1 gene in the following years [26,71,90,107,140,141,142,143,144,145]. Sporadic DGC has shown germline mutations for CDH1 in a hot spot region between exons 7 and 9, whereas genetic alterations scattered over the entire gene length have been observed for HDGC [146].…”