Interpretive Handbook

Test 61814 :
CDH1 Gene, Full Gene Analysis

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 CDH1gene 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 since 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.

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

Confirmation of suspected clinical diagnosis of hereditary diffuse gastric cancer


Identification of familial CDH1 mutation to allow for predictive testing in family members

Interpretation Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

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

Some individuals who have a diagnosis of hereditary diffuse gastric cancer may have a mutation that is not identified by this method (eg, deep intronic mutations, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of a diagnosis of hereditary diffuse gastric cancer. For predictive testing of asymptomatic individuals, it is important to first document the presence of a CDH1 gene mutation in an affected family member.


In some cases, DNA alterations of undetermined significance may be identified.


We strongly recommend that asymptomatic 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.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Contact Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

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: