Test ID: PMS2K
PMS2 Gene, Known Mutation
NY State Approved 
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Diagnostic testing of individuals with suspected diagnosis of Lynch syndrome/ hereditary nonpolyposis colorectal cancer when a mutation in the PMS2 gene has been identified in an affected family member
Predictive testing of at-risk individuals when a mutation in the PMS2 gene has been identified in an affected family member
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Documentation of the specific familial mutations must be provided with the specimen in order to perform this test.
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Polymerase chain reaction (PCR) followed by DNA sequencing or gene dosage analysis by multiplex ligation-dependent probe amplification (MLPA) of the PMS2 gene is utilized to test for the presence of mutations previously identified in an affected family member.
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Hereditary Non-Polyposis Colorectal Cancer
Hereditary Non-Polyposis Colon Cancer
Lynch syndrome
Colon cancer gene testing
Constitutional mismatch repair deficiency
Mismatch repair
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Specimen must arrive within 96 hours of collection.
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.
Forms:
1. Molecular Genetics-Inherited Cancer Syndromes Patient Information Sheet (Supply T519) in Special Instructions
2. 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 (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
No specimen should be rejected. If specimen not received at appropriate temperature or in wrong anticoagulant, include note to laboratory. If questions, contact laboratory.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Ambient (preferred) | |
| Frozen | ||
| Refrigerated | ||
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 is <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 (MSI) and/or immunohistochemistry (IHC) 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 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.
Interpretation Provides information to assist in interpretation of the test results
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.
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 PMS2S/61173 PMS2 Gene, Full Gene Analysis.
Analysis is performed for the familial mutations 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 for instructions for testing patients who have received a bone marrow transplant.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Richards CS, Bale S, Bellissimo DB, ET AL: ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med 2008:10(4):294-300
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 from URL: http://www.ncbi.nlm.nih.gov/books/NBK1211/
Method Description Describes how the test is performed and provides a method-specific reference
DNA sequencing or dosage analysis by multiplex ligation-dependent probe amplification (MLPA) is utilized to test for the presence of a mutation in the PMS2 gene that was previously identified in a family member. Mutation nomenclature is based on GenBank accession number, NM_000535.5.(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)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Friday; 10 am
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81318-PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 33625 | Reason for Referral | 42349-1 |
| 33626 | Result | In Process |
| 33627 | Interpretation | In Process |
| 33628 | Method | 49549-9 |
| 33629 | Amendment | N/A |
| 33630 | Specimen | 31208-2 |
| 33631 | Source | N/A |
| 33632 | Reviewed By | N/A |
| 33633 | Release Date | N/A |
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