HNPCC/Lynch Syndrome (MLH1) Sequencing and Deletion/Duplication
0051650
Ordering Recommendation
Detect germline MLH1 mutations. Use in MMR-deficient carcinoma with suggestive IHC (loss of MLH1 and PMS2 protein), absence of BRAF codon 600 mutation, and normal MLH1 methylation studies.
Mnemonic
MLH1 FGA
Methodology
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
Performed
Varies
Reported
Within 35 days  
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
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
 
 
Available Separately Components Reference Interval
No MLH1 Sequencing By report
No MLHI Deletion/Duplication By report
Interpretive Data
Background Information for HNPCC/Lynch Syndrome (MLH1) Sequencing and Deletion/Duplication:
Characteristics:
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 of MLH1 Mutations:
80 percent lifetime risk of colorectal cancer; 20-60 percent risk for endometrial cancer.
Cause:
Pathogenic germline MLH1, MSH2, MSH6, and PMS2 gene mutations.
Gene Tested:
MLH1
Clinical Sensitivity:
Approximately 45 percent of Lynch syndrome is due to MLH1 mutations.
Methodology:
Bidirectional sequencing of MLH1 coding regions and intron-exon boundaries; multiplex ligation-dependent probe amplification (MLPA) to detect large MLH1 exonic deletions.Analytical Sensitivity & Specificity: 99 percent.
Limitations:
Diagnostic errors can occur due to rare sequence variations. The breakpoints of large deletions/duplications will not be determined. Regulatory region mutations, deep intronic mutations and mutations in genes other than MLH1 will not be detected.

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
 
CPT Code(s)
81292, 81294
Components
Component Test Code*Component Chart NameLOINC
0051651Lynch Syndrome (MLH1) Interpretation 
2001365MLH1 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
  • MLH1gene testing
  • hMLH1genotyping
  • HNPCC
  • Hypermethylation
  • MLH1 genotyping
  • MLH1 Full Gene Analysis (HNPCC/Lynch Syndrome (MLH1) Sequencing and Deletion/Duplication)
  • MLH1 Hypermethylation
  • MLH1germline assay