Lynch Syndrome Panel

This test is used to identify individuals with Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC) syndrome. It analyzes 5 genes: MLH1, MSH2, MSH6, PMS2, and EPCAM. These genes encode the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, as well as EPCAM (deletions in the 3’ end of EPCAM disrupt transcription of MSH2).

Sample reports and information regarding the specific variants analyzed for each gene are available on the website QuestHereditaryCancer.com. 

If a familial mutation has been detected by sequencing or deletion/duplication studies, the Hereditary Cancer Single Site(s) test (test code 93945) may be considered. Official test results of the family member must be available for laboratory review.

For more information, please visit the website QuestHereditaryCancer.com. To discuss a family history with a Quest Diagnostics genomic science specialist, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463).

In rare cases, previous testing may indicate only testing one of the genes. The following single-gene tests are available:

• Lynch Syndrome, MLH1 Sequencing and Deletion/Duplication (test code 91460)
• Lynch Syndrome, MSH2 Sequencing and Deletion/Duplication (Including EPCAM) (test code 91471)
• Lynch Syndrome, MSH6 Sequencing and Deletion/Duplication (test code 91458)
• Lynch Syndrome, PMS2 Sequencing and Deletion/Duplication (test code 91457) 

Generally, this test may be indicated for individuals with any of the following¹:

• A personal or family history of colorectal, endometrial, ovarian, gastric, pancreatic, ureter and renal pelvis, brain (usually glioblastoma), biliary tract, and/or small intestinal cancers, sebaceous carcinomas, and keratoacanthomas
• A personal history of colorectal or endometrial cancer with evidence of MMR deficiency, demonstrated either by microsatellite instability (MSI) or by loss of MMR protein expression via IHC analysis  
• A personal history of colorectal tumor with MSI-high histology (ie, presence of tumor-infiltrating lymphocytes, Crohn-like lymphocytic reaction, mucinous/signet ring differentiation, or medullary growth pattern)
• A ≥2.5% risk of having a pathogenic variant in an MMR gene based on predictive models (ie, PREMM5, MMRpro, MMRpredict)¹

Informed consent following genetic counseling is strongly recommended. Whenever possible, consider testing the person in the family with the youngest age at the time of diagnosis of a Lynch syndrome–associated cancer.

For more information or to discuss a family history with a Quest genomic science specialist, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463).

The right time depends on the individual. An individual’s current medical status, personal experience with cancer, treatment or screening plan, and general readiness for genetic information all influence the decision to be tested. Having an open dialogue with individuals about these topics can assist with shared decision-making. Additionally, consider referring individuals to a clinical genetic counselor for a thorough review of the individual’s family history and discussion of testing options.

Find a local genetic counselor by visiting FindAGeneticCounselor.com.

Upon receipt of a fully completed order, the Quest team will verify coverage with the patient’s healthcare insurance plan. Quest will notify the ordering healthcare professional and/or the patient before test initiation to discuss options for continuation or cancellation of the test if Quest identifies that patient does not meet the qualifications for test coverage. Please note that orders lacking complete information will not be processed.

For most tests, results will be completed 14 to 21 days after receipt of the sample in the laboratory and completion of preauthorization. For tests with 12 or more genes, the turnaround time is 21 to 30 days.

Please note that an additional 7 to 10 days for confirmation of copy number variants (CNVs) by an orthogonal method if needed. Turnaround time may vary based on delays caused by incomplete orders or insurance authorizations.

Individuals with a positive result have a pathogenic or likely pathogenic variant(s) detected in the MLH1, MSH2, MSH6, PMS2, and/or EPCAM gene(s), and a diagnosis of Lynch syndrome.¹ A positive result does not mean that an individual has a diagnosis of cancer.

Pathogenic and likely pathogenic variants in these genes have an autosomal dominant pattern of inheritance, meaning that a first-degree relative has a 50% chance of having the same result. Though rare, if an individual inherits 2 different mutations (1 from each parent) in the same gene, they have a diagnosis of autosomal recessive constitutional MMR deficiency (CMMRD).

The National Comprehensive Cancer Network (NCCN^®) provides up-to-date surveillance and management recommendations for individuals with a positive result.¹

A negative result means that a pathogenic or likely pathogenic variant was not detected in MLH1, MSH2, MSH6, or PMS2, and a deletion in 3’ end of EPCAM was not detected. For more information regarding specific genetic variants analyzed in this assay, please refer to the methods and limitations section of the genetic testing report. Implications of this result depend on the situation:

Individual with previously diagnosed cancer:

An individual’s risk of recurrence or a related new cancer is based on their personal and family histories of cancer. In some instances, it may be appropriate to test for other hereditary forms of cancer.

Please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to discuss possible additional studies with a genomic science specialist.

Individual without previously diagnosed cancer but with a family history of cancer:

An individual’s risk of cancer is based on their personal and family histories of cancer. Testing an affected family member may further inform this risk assessment.¹ In some instances, it may be appropriate to test for other hereditary forms of cancer.

Please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to discuss possible additional studies with a genomic science specialist. 

A VUS result means that the variant has not been previously described in the literature or that the clinical significance is unclear based upon currently available evidence. Medical management decisions should be based on personal and family history. Family studies may help to learn more about the clinical significance of this variant. The classification and interpretation of the variant(s) identified reflect the current state of Quest’s understanding at the time of the report.

Variant classification and interpretation are subject to professional judgment and may change for a variety of reasons including, but not limited to, updates in classification guidelines and availability of additional scientific and clinical information. It is important to check in with the laboratory annually for variant updates because new information regarding the variant and classification may become available over time.

Please visit QuestDiagnostics.com/VariantIQ for information about variant classification. For questions, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to speak with a genomic science specialist.