Hereditary diffuse gastric cancer (HDGC) – CDH1 gene

Hereditary diffuse gastric cancer is a highly invasive cancer. Patients typically manifest the first symptoms at the age of ~40 years and men have a cumulative risk of 67% for cancer by the age of 80 years, while women have a cumulative risk of 83%. The disease is caused by mutations of the CDH1 gene, found in all ethnic groups, but is rarer in countries with high rates of sporadic gastric cancer, such as Japan and Korea. About 10% of patients with this type of hereditary cancer have a family history of the disease, and about 1-3% of cases carry inherited mutations of the CDH1 gene. Finally, mutations of the CDH1 gene can also cause lobular breast cancer in women.

The International Gastric Cancer Linkage Consortium (IGCLC) recently published recommendations for monitoring this type of cancer (Fitzgerald, et al J Med Genet 2010; 47: 436-444), which is recommended in cases:

  • With two cases of gastric cancer in the family, one affected member under 50 years with confirmed diffuse gastric cancer (DGC)
  • With three confirmed cases in first or second degree relatives, regardless of age
  • With sporadic diffuse gastric cancer before the age of 40 years, and
  • With a personal or family history of diffuse gastric cancer and/or lobular breast cancer, where one of the types has been diagnosed before the age of 50 years.

We perform DNA sequence analysis, via Next Generation Sequencing (NGS) on a Genome Analyzer – Ion Proton platform, of all exons and intron-exon junctions/splice sites of the CDH1 gene, as well as deletion/duplication analysis through MLPA (non-detectable by DNA sequencing), allowing us to detect >98% of all pathogenic mutations of the gene.

Please note that the test is in a position to detect germline only (hereditary) mutations from a peripheral blood sample, while a tumor biopsy sample is required to detect somatic mutations, typically present in mosaicism.

See also genomic testing for gastrointestinal cancers – 21 genes NGS panel