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Test ID: PMS2Z PMS2 Gene, Full Gene Analysis

Useful For

Establishing a diagnosis of Lynch syndrome/hereditary nonpolyposis colorectal cancer

 

Determining whether absence of PMS2 protein in tumor tissue, as demonstrated by immunohistochemistry, is associated with a germline mutation in the affected individual

 

Identification of familial PMS2 mutation to allow for predictive testing in family members

Testing Algorithm

See Hereditary Nonpolyposis Colorectal Cancer Testing Algorithm in Special Instructions.

Method Name

Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis and Gene Dosage Analysis by Multiplex Ligation-Dependent Probe Amplification (MLPA)

Reporting Name

PMS2 Gene, Full Gene Analysis

Specimen Type

Varies


Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Necessary Information


Submit the required form with the specimen.



Specimen Required


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.


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, and 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 and 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 and/or immunohistochemistry for the presence or absence of defective DNA mismatch repair. Tumors that demonstrate absence of expression of PMS2 are more likely to have a germline mutation in the PMS2 gene.

Reference Values

An interpretative 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. Vaughn CP, Hart J, Samowitz WS, Swensen JJ: Avoidance of pseudogene interference in the detection of 3'deletions in PMS2. Hum Mutat 2011;32:1063-1071

3. Senter L, Clendenning M, Sotamaa K, et al: The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 2008;135:419-428

4. Clendenning M, Hampel H, LaJeunesse J, et al: Long-range PCR facilitates the identification of PMS2-specific mutations. Hum Mutat 2006;27(5):490-495

5. Vasen HFA, Moslein G, Alonso A, et al: Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet 2007;44:353-362

6. Lynch Syndrome-GeneReviews-NCBI Bookshelf. Available at www.ncbi.nlm.nih.gov/books/NBK1211/

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

81317-PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

 

81319-PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants

LOINC Code Information

Test ID Test Order Name Order LOINC Value
PMS2Z PMS2 Gene, Full Gene Analysis In Process

 

Result ID Test Result Name Result LOINC Value
53540 Result Summary 50397-9
53541 Result In Process
53542 Interpretation In Process
53543 Additional Information 48767-8
53544 Specimen In Process
53545 Source 31208-2
53546 Released By No LOINC Needed

Forms

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

2. Lynch Syndrome (PMS2) 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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