Detect germline MSH2 variants. Use in MMR-deficient carcinoma with suggestive IHC results (loss of MSH2 and MSH6 proteins). Includes evaluation of EPCAM exon 9 deletions and 10 Mb inversion of MSH2 exons 1-7.
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
New York DOH Approval Status
Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 2 mL)
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
|No||MSH2 Full Gene Sequencing||By report|
|No||MSH2 Deletion/Duplication/Inversion||By report|
Background Information for HNPCC/Lynch syndrome (MSH2) 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 pathogenic mismatch repair gene variants.
Inheritance: Autosomal dominant.
Penetrance: 80 percent lifetime risk of colorectal cancer; 20-60 percent risk for endometrial cancer.
Cause: Pathogenic germline MLH1, MSH2, MSH6, and PMS2 gene variants.
Gene tested: MSH2
Clinical Sensitivity: 40 percent of Lynch syndrome is due to pathogenic MSH2 variants.
Methodology: Bidirectional sequencing of MSH2 coding regions and intron-exon boundaries; multiplex ligation-dependent probe amplification (MLPA) to detect large exonic deletions and duplications of MSH2, EPCAM (TACSTD1) exon 9 and the 10Mb MSH2 exons1-7 inversion.
Analytical Sensitivity & Specificity: 99 percent.
Test Limitations: Diagnostic errors can occur due to rare sequence variations. The breakpoints of large deletions/duplications/inversions will not be determined. Deep intronic and regulatory region variants will not be detected. Variants in genes other than MSH2 and TACSTD1, as described above, will not be detected. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.
This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
Laboratory Developed Test (LDT)
|Component Test Code*||Component Chart Name||LOINC|
|0051653||MSH2 Full Gene Analysis|
|2001367||MSH2 FGA Specimen|
- MSH2 gene testing
- MSH2 genotyping
- MSH2 germline mutation assay