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CDH1
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Interpretation 2291
Tier 2
CDH1
Variants
CDH1 D400V
Primary Sites
Appendix
Tumor Types
Carcinoma
Interpretation

CDH1 on 16q22.1 encodes E-cadherin which functions in intercellular adhesion. E-cadherin is involved in transmitting chemical signals and controlling cell maturation and movement, and acts as a tumor suppressor. A lack of functional E-cadherin impairs cell adhesion and increases the likelihood of invasion and metastasis of tumor cells. CDH1 is altered by mutation or deletion in various cancers and loss of E-cadherin has been demonstrated in a variety of sporadic cancer types including breast cancer, gastric cancer, colorectal cancer, and esophageal cancer. Along with point mutations and loss of heterozygosity (LOH), epigenetic silencing by hypermethylation of the CDH1 promoter has been associated with the loss of E-cadherin gene expression during cancer progression. Individuals with a germline CDH1 mutation have an increased risk of developing diffuse gastric cancer and breast cancer. More than 100 different pathogenic germline mutations are distributed throughout the CDH1 gene including splice-site sequences and have been found to cause a familial cancer disorder called hereditary diffuse gastric cancer (HDGC). Somatic CDH1 alterations are also found in approximately 30% of all patients with gastric cancers, both diffuse and intestinal types. Genetic alterations of CDH1 have been identified in 4% of colorectal adenocarcinomas. CDH1 D400V lies within the Cadherin domain 3 of the Cdh1 protein (UniProt.org) and mutations in this locus has been reported previously.

Citations
  1. Hansford S, et al. Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. JAMA Oncol 2015;1(1):23-32
  2. Corso G, et al. Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. J Clin Oncol 2013;31(7):868-75
  3. van der Post RS, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet 2015;52(6):361-74
  4. Yoshiura K, Kanai Y, Ochiai A, Shimoyama Y, Sugimura T, Hirohashi S. Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7416-9.
  5. Pharoah PD, Guilford P, Caldas C; International Gastric Cancer Linkage Consortium. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin)mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology. 2001 Dec;121(6):1348-53.
  6. Elzagheid A, Buhmeida A, Laato M, El-Faitori O, Syrjanen K, Collan Y, Pyrhonen S. Loss of E-cadherin expression predicts disease recurrence and shorter survival in colorectal carcinoma. APMIS. 2012 Jul;120(7):539-48.
  7. Comprehensive TCGA PanCanAtlas (https://gdc.cancer.gov/about-data/publications/pancanatlas).
Last updated: 2019-01-22 18:31:31 UTC
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