These results support the conclusion that CDH1 c.1679C>G (p.T560R) variant is a pathogenic mutation and contributes to HDGC through disruption of normal splicing.
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.
Hereditary diffuse gastric cancer (HDGC) syndrome is caused by germline mutations in the CDH1 gene and carries a lifetime gastric cancer risk of approximately 70 % in men and 56 % in women.
Hereditary diffuse gastric cancer has an early onset and poor prognosis, therefore, individuals who carry a pathogenic (CDH1) mutation in the E-cadherin gene (CDH1) are offered endoscopic surveillance and advised to undergo prophylactic total gastrectomy (PTG) in their early to mid-twenties.
The gene responsible for HDGC is CDH1, also known as E-cadherin, a germline mutation conferring an 80% risk of developing gastric cancer during the lifetime of the carrier.
Second, we find that many cancer-associated germline missense mutations in the E-cadherin gene in patients with hereditary diffuse gastric cancer selectively affect the mechanism of inside-out cell surface regulation without inhibiting basic E-cadherin adhesion function.
There were 18 pathogenic CDH1 mutations in 499 families (4%); 16 of these mutations were detected in the 118 families who met the HDGC criteria for testing.
Hereditary diffuse gastric cancer syndrome: improved performances of the 2015 testing criteria for the identification of probands with a CDH1 germline mutation.
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).
A striking example is the presence of CDH1 (E-cadherin gene) germline missense variants in hereditary diffuse gastric cancer (HDGC), which represent a clinical burden for genetic counseling and surveillance of mutation carriers and their families.