• Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit



Arc-1; Arc-1, CD324, CDHE, ECAD, LCAM, UVO; CD324; CDHE; ECAD; LCAM; UVO

Associated disorders

The CDH1 gene is associated with autosomal dominant hereditary diffuse gastric cancer (HDGC) syndrome (MedGen UID: 310839), lobular breast cancer (PMID: 11729114, 17545690, 25979631), and possibly an increased risk for colon cancer (PMID: 10072428).

The CHD1 gene encodes the protein E-cadherin, a protein embedded in the cell membrane that contributes to cell-cell adhesion, primarily in epithelial cells. Loss of E-cadherin function due to pathogenic variants in CDH1 impairs the ability of epithelial cells to adhere to each other and predisposes them to become metastatic and invade other tissues during cancer progression. The lack of cell-cell adhesion contributes to the diffuse nature of the resulting adenocarcinoma.

CDH1 heterozygote
MedGen UID: 310839

Clinical condition
Hereditary diffuse gastric cancer (HDGC) syndrome is an adult-onset hereditary cancer predisposition syndrome characterized by an increased risk of gastric cancer and lobular breast cancer.

Diffuse gastric cancer is a type of adenocarcinoma that infiltrates and thickens the stomach wall without forming a distinct tumor mass. Signet ring cells are often observed throughout the stomach wall. Symptoms typically present in advanced disease and can include stomach pain, nausea, vomiting, difficulty swallowing, decreased appetite, and weight loss. The risk of gastric cancer is 56–83% for women and 67–80% for men (PMID: 11729114, 20591882, 25979631). Women with HDGC have a 39–52% chance of developing lobular breast cancer, with the average age at diagnosis of 53 years (PMID: 17545690, 11729114, 25979631). Evidence suggests that orofacial clefts may also be a feature of HDGC (PMID: 23124477). Additionally, there are data suggesting an increased risk of colorectal cancer associated with HDGC, though these data are limited and emerging (PMID: 26182300, 10072428, 25979631). An individual with a CDH1 pathogenic variant will not necessarily develop cancer in his/her lifetime, but the risk for cancer is increased over the general population risk.

Gene information
CDH1 is a tumor-suppressor gene that provides instructions for making epithelial cadherin, or E-cadherin. This protein is found within the membranes surrounding epithelial cells. E-cadherin belongs to a family of proteins called cadherins that play a role in cell adhesion, signal transduction, controlling cell maturation and movement, and regulating the activity of certain genes (Genetics Home Reference. CDH1. Accessed January 2017, UniProt consortium, UniprotKB – P12830 (CADH1_HUMAN). Accessed January 2017).

Hereditary diffuse gastric cancer (HDGC) syndrome has autosomal dominant inheritance. This means that an individual with a pathogenic variant in CDH1 has a 50% chance of passing the condition on to their offspring. Once a pathogenic mutation is detected in an individual, it is possible to identify at-risk relatives who can pursue testing for this specific familial variant. Many cases are inherited from a parent, but some cases can occur spontaneously (i.e., an individual with a pathogenic variant has parents who do not have it). An individual with a variant in CDH1 has a 50% risk of passing that variant on to offspring.

Breast Cancer Guidelines:
Management guidelines for individuals with HDGC have been developed by the National Comprehensive Cancer Network® (NCCN®) ( NCCN. Genetic/Familial High Risk Assessment: Breast and Ovarian. Version 2.2017, accessed January 10, 2017., NCCN. Gastric. Version 3.2016, accessed January 10, 2017, PMID: 20591882, 20301318). The following has been recommended for breast management:

  • annual mammography beginning at age 30, with modification as appropriate based on family history or specific gene mutation
  • consider annual breast MRI with contrast beginning at age 30, with modification as appropriate based on family history or specific gene mutation
  • consider risk reducing mastectomy based on family history
  • referral to genetic counseling

Gastric Guidelines
The following is recommended for gastric management (NCCN. Genetic/Familial High-Risk Assessment: Gastric. Version 3.2016; PMID: 20591882, 20301318)

  • total gastrectomy between the ages of 18 and 40 due to the high mortality rate of gastric cancer and the low rate of detection by endoscopic screening
    • Prophylactic gastrectomy is not recommended prior to 18 years of age but may be considered for those with family members diagnosed with gastric cancer prior to age 25.
    • Baseline endoscopy with multiple random biopsies is recommended prior to gastrectomy to assess for the presence of macroscopic tumor foci or other factors that may lead to a more complex surgery.
    • Careful pathologic examination and sampling should occur (PMID: 25979631).
    • A D2 lymph node dissection is not necessary for prophylactic total gastrectomy.

Multidisciplinary care should be incorporated pre- and post-surgery and should include the gastroenterologist, surgeon, pathologists, and nutritionists. The individual’s physical and psychological fitness, as well as age, nutrition, lifestyle, and family support, must be considered along with an assessment of the emotional effects a total gastrectomy will have.

Upper endoscopy is proposed for those with HDGC who do not opt for prophylactic gastrectomy or for whom gastrectomy has been deferred (NCCN. Genetic/Familial High-Risk Assessment: Gastric. Version 3.2016). Endoscopic screening including a detailed, 30-minute endoscopic examination of the gastric mucosa with multiple random biopsies and biopsies of subtle lesions is recommended at six- to twelve-month intervals (National Comprehensive Cancer Network. Gastric Cancer. Version 3.2016; PMID: 10593993). Also, it is recommended that this procedure be performed at a center that has experience with HDGC. Microscopic tumor foci have been detected on most prophylactic gastrectomy pathology in those with HDGC who have recently undergone endoscopic screening, highlighting the limitations of endoscopic screening in these high-risk individuals (PMID: 17522512, 20301318). Affected individuals should be counseled of the high risks of mortality from delaying prophylactic gastrectomy (PMID: 24472763).

Colon Surveillance
There is currently no conclusive evidence that the risk for colorectal cancer is elevated in those with a pathogenic variant in CDH1. However, Fitzgerald et al. have suggested enhanced colorectal surveillance for the subset of HDGC families with colorectal cancer diagnoses (PMID: 25979631, 20591882). Specifically, they recommend colonoscopy screening beginning at age 40 or 10 years younger than the youngest diagnosis of colon cancer, whichever is younger, and repeated at intervals of 3–5 years (PMID: 25979631).

An individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors, including personal medical history, family history, and any available genetic information that may result in a personalized plan for cancer prevention and surveillance.

Knowing if a pathogenic CDH1 variant is present is advantageous. At-risk relatives can be identified, enabling pursuit of a diagnostic evaluation. Further, the available information regarding hereditary cancer susceptibility genes is constantly evolving and more clinically relevant data regarding CDH1 are likely to become available in the near future. Awareness of this cancer predisposition encourages patients and their providers to inform at-risk family members, to diligently follow condition-specific screening protocols, and to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information.

Review date: January 2017

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CDH1 NM_004360.3