HNPCC/Lynch Syndrome (PMS2) Sequencing and Deletion/Duplication
0051737
Ordering Recommendation
Detect germline PMS2 mutations. Use in MMR-deficient carcinoma with suggestive IHC (isolated loss of PMS2 protein).
Mnemonic
PMS2 FGA
Methodology
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
Performed
Varies
Reported
Within 35 days  
New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
  
Collect
Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B).  
Specimen Preparation
Transport 3 mL whole blood. (Min: 1 mL)  
Storage/Transport Temperature
Refrigerated.  
Unacceptable Conditions
  
Remarks
  
Stability
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable  
Reference Interval
   
Interpretive Data
Background information for HNPCC/Lynch Syndrome (PMS2) Sequencing and Deletion/Duplication
Characteristics of Lynch Syndrome:
Increased risk of colorectal and extra-colonic cancers including endometrial, renal pelvis, ureter, ovary, stomach, small intestine and hepatobiliary tract.
Incidence:
1-2 percent of colorectal cancer is due to mismatch repair gene mutations.
Inheritance:
Autosomal dominant.
Penetrance:
Unknown for PMS2 mutations.
Cause:
Pathogenic germline MLH1, MSH2, MSH6, and PMS2 gene mutations.
Gene tested:
PMS2
Clinical Sensitivity:
Less than 5 percent of Lynch syndrome cases are due to PMS2 mutations.
Methodology:
Bidirectional sequencing of PMS2 coding regions and intron-exon boundaries; multiplex ligation-dependent probe amplification (MLPA) to detect large PMS2 exonic deletions.
Analytical Sensitivity & Specificity:
99 percent.
Limitations:
Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations and deep intronic mutations will not be detected. Mutations in genes other than PMS2 are not evaluated.

This test is performed pursuant to an agreement with Roche Molecular Systems, Inc.





See Compliance Statement C: www.aruplab.com/CS
Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test; however, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
 
Note
Suspected deletions or duplications in exons 12-15 require additional sequencing to exclude pseudogene copy number variants.  Additional charges apply.
CPT Code(s)
81317, 81319
If pseudogene analysis is performed, add: 81479
Components
Component Test Code*Component Chart NameLOINC
0051738Lynch Syndrome (PMS2) Interpretation 
2001372PMS2 FGA Specimen 
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • HNPCC
  • PMS2 gene testing
  • PMS2 genotyping
  • PMS2 germline assay