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Test ID: MLH1Z MLH1 Gene, Full Gene Analysis

Useful For

Determining whether absence of MLH1 protein, by immunohistochemistry in tumor tissue, is associated with a germline mutation in the affected individual

 

Establishing a diagnosis of Lynch syndrome/hereditary nonpolyposis colorectal cancer

 

Identification of familial MLH1 mutation to allow for predictive testing in family members

Additional Tests

Test ID Reporting Name Available Separately Always Performed
COLAB Hereditary Colon Cancer CGH Array Yes, (Order FMTT) Yes

Testing Algorithm

When this test is ordered, comparative genomic hybridization array will always be performed at an additional charge.

 

See Hereditary Nonpolyposis Colorectal Cancer Testing Algorithm in Special Instructions.

Method Name

Polymerase Chain Reaction (PCR) Amplification/DNA Sequencing

Reporting Name

MLH1 Gene, Full Gene Analysis

Specimen Type

Varies


Shipping Instructions


Specimen preferred to arrive within 96 hours of draw.



Necessary Information


 



Specimen Required


Patient Preparation: 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.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Additional Information: Prior Authorization is available for this test. Submit the required form with the specimen.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer or HNPCC) is an autosomal dominant hereditary cancer syndrome associated with germline mutations in the mismatch repair genes, MLH1, MSH2, MSH6, and PMS2. Deletions within the 3-prime end of the EPCAM gene have also been associated with Lynch syndrome, as this leads to inactivation of the MSH2 promoter.

                                               

Lynch syndrome is predominantly characterized by significantly increased risks for colorectal and endometrial cancer. The lifetime risk for colorectal cancer is highly variable and dependent on the gene involved. The risk for colorectal cancer-associated MLH1 and MSH2 mutations (approximately 50%-80%) is generally higher than the risks associated with mutations in the other Lynch syndrome-related genes. The lifetime risk for endometrial cancer (approximately 25%-60%) is also highly variable. Other malignancies within the tumor spectrum include gastric cancer, ovarian cancer, hepatobiliary and urinary tract carcinomas, and small bowel cancer. The lifetime risks for these cancers are <15%. Of the 4 mismatch repair genes, mutations within the PMS2 gene confer the lowest risk for any of the tumors within the Lynch syndrome spectrum.

 

Several clinical variants of Lynch syndrome have been defined. These include Turcot syndrome, Muir-Torre syndrome, and homozygous mismatch repair mutations (also called constitutional mismatch repair deficiency syndrome). Turcot syndrome and Muir-Torre syndrome are associated with increased risks for cancers within the tumor spectrum described, but also include brain/central nervous system malignancies and sebaceous carcinomas, respectively. Homozygous mismatch repair mutations, characterized by the presence of biallelic deleterious mutations within a mismatch repair gene, are associated with a different clinical phenotype defined by hematologic and brain cancers, cafe au lait macules, and childhood colon or small bowel cancer.

 

There are several strategies for evaluating individuals whose personal or family history of cancer is suggestive of Lynch syndrome. One such strategy involves testing the tumors from suspected individuals for microsatellite instability (MSI) and immunohistochemistry (IHC) for the presence or absence of defective DNA mismatch repair. Tumors that demonstrate absence of expression of MLH1 and PMS2 are more likely to have a germline mutation in the MLH1 gene.

Reference Values

An interpretive report will be provided.

Interpretation

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

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Baudhuin LM, Burgart LJ, Lentovich O, Thibodeau SN: Use of microsatellite instability and immunohistochemistry testing for the identification of individuals at risk for Lynch Syndrome. Fam Cancer 2005;4:255-265

3. Umar A, Baland CR, Terdiman JP, et al: Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004;261-268

4. Lynch HT, de le Chapelle A: Hereditary colorectal cancer. N Engl J Med 2003;348:919-932

5. International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer. Mutation Database. Available at www.insight-group.org/

Day(s) and Time(s) Performed

Performed weekly, Varies

Analytic Time

14 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81292-MLHI1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

81228-Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number variants (eg, Bacterial Artificial Chromosome [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MLH1Z MLH1 Gene, Full Gene Analysis In Process

 

Result ID Test Result Name Result LOINC Value
53576 Result Summary 50397-9
53577 Result In Process
53578 Interpretation 69047-9
53579 Additional Information 48767-8
53580 Specimen 31208-2
53581 Source 31208-2
53582 Array Billed? No LOINC Needed
53583 Released By No LOINC Needed

Forms

1. Molecular Genetics: Inherited Cancer Syndromes Patient Information (T519) in Special Instructions

2. Lynch Syndrome (MLH1) Full Gene Analysis Prior Authorization Ordering Instructions in Special Instructions

3. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

4. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

Oncology Test Request Form (T729) (http://www.mayomedicallaboratories.com/it-mmfiles/oncology-request-form.pdf)

Gastroenterology and Hepatology Test Request Form (T728) (http://www.mayomedicallaboratories.com/it-mmfiles/gastroenterology-and-hepatology-test-request.pdf)

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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