CDH1 mutation testing in families with a history of gastric cancer and prophylactic gastrectomy in mutation-positive patients are recommended for the management of HDGC.
Participants included one 37-year-old man with multiple polyps in his stomach and a family history of stomach cancer, one 18 year-old man with a confirmed CDH1 mutation and a family history of stomach cancer, and one 33-year-old man with confirmed metastatic gastric adenocarcinoma.
We detected the epidermal growth factor receptor L858R, MSH2 R929* and telomerase reverse transcriptase amplification in the lung cancer specimen; CDH1 c.1320+1G>T mutation in the gastric cancer (GC) specimen; and MLH1 c.1896+5G>A germline mutation in the lung and GC specimens by 450 cancer-related gene mutations detection using next-generation sequencing technology.
In our area, in which a high rate of familial aggregation was demonstrated, the lack of germ line mutation of TP53 together with the infrequency of mutation of E-cadherin gene seem to limit the role of genetic predisposition in the development of gastric cancer.
Gastric cancer (GC) is considered to be one of the leading cancers in East Asians, and mutations in the CDH1 gene and the reduced expression of E-cadherin are the most frequent genetic alterations in gastric cancer.
In this perspective, we investigated whether hypermethylation in the CDH1 promoter region is correlated with poor prognosis of patients with surgically resected, node-positive, diffuse gastric cancer.
Germline inactivation of the E-cadherin gene (CDH1) is associated with hereditary diffuse gastric cancer (HDGC), a rare autosomal dominant syndrome predisposing to both diffuse gastric cancer (DGC) and lobular breast cancer (LBC).
Thirty-six percent (5 of 14) of the families with a documented DGC diagnosed before the age of 50 and other cases of gastric cancer carried CDH1 germ line mutations.
Heterozygotes with the CDH1 mutation have a 70-80% chance of developing gastric cancer and once patients have invasive, symptomatic disease there is a high associated morbidity and mortality.
The risk of development of gastric cancer is high in families affected b-y these syndromes, but only hereditary diffuse gastric cancer is genetically explained (caused by germline alterations of CDH1, which encodes E-cadherin).
Laser capture microdissection combined with real-time polymerase chain reaction and Western blot were used to determine the expressions of Bmi-1, the cellular homologue of avian myelocytomatosis virus (c-Myc), enhancer of Zeste homolog 2 (EZH2), phosphatase and tensin homologue (PTEN) and epithelial cadherin (E-cadherin) in 20 GC specimens and the adjacent non-cancerous gastric tissues.
In conclusion, our results indicated that plasma CDH1 levels may serve as a risk marker against gastric cancer and variant genotypes of rs26160 and rs17690554 may contribute to the etiology of diffuse gastric cancer in this study.
An overview of the various pathways of importance in gastric cancer, as discovered through in-vitro, primary cancer and mouse model studies, is presented and the clinical importance of CDH1 mutations is discussed.