Interpretive Handbook

Test 61815 :
CDH1 Gene, Known Mutation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant hereditary cancer syndrome associated with germline mutations in the CDH1 gene that encodes the protein E-cadherin. HDGC is predominantly characterized by increased susceptibility to diffuse gastric cancer and lobular breast cancer. HDGC is highly penetrant as the risk for developing gastric cancer is 80% by age 80. Women also have an approximately 40% to 60% risk of breast cancer by age 80. Colorectal cancer has been reported in individuals with germline CDH1 mutations however, the specific lifetime risk for colorectal cancer is unknown.


The International Gastric Cancer Linkage Consortium proposes clinical criteria for the selection of individuals who are at increased risk of having a germline CDH1 mutation as follows: 1) two or more cases of diffuse gastric cancer (histopathological confirmation in at least 1 case) in first- or second-degree relatives in which at least 1 individual is diagnosed prior to age 50; 2) three or more documented cases of diffuse gastric cancer in first- or second-degree relatives regardless of age of onset; 3) individuals diagnosed with diffuse gastric cancer before the age of 40 regardless of family history; 4) personal or family history of diffuse gastric cancer and lobular breast cancer in first- and second-relatives with at least 1 diagnosis occurring before age 50.


Note: This test is appropriate for predictive testing in families in which a point mutation or small insertion/deletion/duplication has been identified. SDEL / Single-Gene Large Deletion and Duplication Analysis is appropriate for predictive testing in families in which a large deletion or duplication (whole exon or multi-exon) has been identified. If a familial mutation has not been previously identified, CDH1S / CDH1 Gene, Full Gene Analysis is more appropriate.

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnostic testing of individuals with suspected diagnosis of hereditary diffuse gastric cancer when a mutation in the CDH1 gene has been identified in an affected family member


Predictive testing of at-risk individuals when a mutation in the CDH1 gene has been identified in an affected family member

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be performed. If a familial mutation has not been previously identified, order CDH1S / CDH1 Gene, Full Gene Analysis.


Analysis is performed for the familial mutation provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with hereditary cancer syndromes.


We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.


Predictive testing of an asymptomatic child is not recommended.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false paternity, could lead to erroneous interpretation of results.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 for instructions on testing patients who have received a bone marrow transplant.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med 2008:10(4):294-300

2. Lindor NM, McMaster ML, Lindor CJ, et al: Concise handbook of familial cancer susceptibility syndromes-second edition. J Natl Cancer Inst Monogr 2008;(38):1-93

3. Fitzgerald RC, Hardwick R, Huntsman D, et al: Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 2010;47:436-444

4. Kaurah P, Huntsman DG: Hereditary Diffuse Gastric Cancer. GeneReviews 2011. Available from URL: