Interpretive Handbook

Test 84304 :
MYH Gene Analysis for Multiple Adenoma, Y165C and G382D

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

Biallelic germline mutations in the MYH gene (official symbol MUTYH) cause MYH-associated polyposis (MAP) syndrome, an autosomal recessive form of inherited colorectal cancer. Approximately 15% to 20% of all colorectal cancer cases are thought to be due to heritable genetic causes. The 2 most common forms of hereditary colorectal cancer are familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). FAP accounts for <1% of all colorectal cancer cases and HNPCC accounts for approximately 2% to 3% of all colorectal cancer. The proportion of inherited colorectal cancer cases attributable to MAP is not known at this time.


Phenotypic overlap exists between MAP and FAP. However, patients with MAP tend to develop fewer adenomatous polyps (generally <100) than patients with classical FAP, who generally develop hundreds to thousands of polyps. Patients with biallelic MYH mutations are at risk for colorectal cancer and other extracolonic manifestations (upper gastrointestinal tumors, congenital hyperpigmentation of the retinal epithelium) similar to those observed in patients with FAP. Although patients with MAP typically present with multiple polyps, literature suggests that biallelic mutations have been seen in patients with early onset colorectal cancer. Therefore, screening for MYH should be considered in patients with early onset colorectal cancer in whom no DNA mismatch repair (MMR) defect has been identified.


Literature suggests that monoallelic carriers may be at slightly increased risk for colon cancer, upper gastrointestinal cancer, and other tumors. Approximately 1% to 2% mixed European Caucasian individuals are predicted to carry an MYH mutation. Therefore, the reproductive partners of monoallelic and biallelic carriers should be offered carrier screening to adequately assess the risk of their offspring having MAP.


The MYH gene is located on chromosome 1 and encodes a base excision repair protein that functions to repair oxidative DNA damage. This assay provides direct analysis of the Y165C and G382D mutations in the MYH gene. These 2 mutations account for approximately 85% of the disease-causing MYH mutations in affected mixed European Caucasian individuals. Refer to Hereditary Colorectal Cancer: Adenomatous Polyposis Syndromes, Mayo Medical Laboratories Communique 2004 Sep;29(9) for more information regarding diagnostic strategy. Also see Colonic Adenomatous Polyposis Syndromes Testing Algorithm in Special Instructions.

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

Determining whether the clinical phenotype of multiple colorectal adenomas is due to biallelic MYH mutations in the affected individual


Predictive testing and familial risk assessment by carrier screening for multiple colorectal adenomatous polyps when an MYH mutation has been identified in an affected family member

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

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

This assay will not detect all of the mutations that cause MAP. Therefore, the absence of a detectable mutation(s) does not rule out the possibility that an individual is a carrier of or affected with this disease.


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.


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.


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


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


It is important to first document the presence of identifiable MYH mutation(s) in an affected family member prior to performing predictive testing.


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

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. Sieber OM, Lipton L, Crabtree M, et al: Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 2003;348(9):791-799

2. Wang L, Baudhuin LM, Boardman LA, Steenblock KJ, et al: MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. Gastroenterology 2004;127(1):9-16

3. Croitoru M, Cleary S, Di Nicola N, et al: Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk. J Natl Cancer Inst 2004;96:1631-1634