Lynch Syndrome, PMS2 Sequencing and Deletion/Duplication

This test is used to identify individuals with Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC) syndrome. It detects single-nucleotide variants, deletions, and duplications in the PMS2 gene, which encodes the mismatch repair protein PMS2. Sample reports and information regarding the specific variants analyzed are available on our website QuestHereditaryCancer.com.

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

When immunohistochemical (IHC) analysis of mismatch repair proteins has been performed on certain tumor types, and loss of protein(s) was identified, germline testing of the corresponding gene(s) may be appropriate.¹

When there is a suspicion of Lynch syndrome but the familial mutation is not known and IHC analysis has not been performed, then testing for all Lynch genes may be considered with a multigene panel.  Multigene panels that include all Lynch genes include Lynch Syndrome Panel [test code 91461], Guideline-based Hereditary Cancer Panel [test code 38611] and Comprehensive Hereditary Cancer Panel [test code 38600].

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

Generally, this test may be indicated for individuals with a personal history of a Lynch syndrome–related cancer when IHC analysis of mismatch repair proteins has been performed on the tumor and is suggestive of an inherited mutation in the PMS2 gene.¹ Lynch syndrome-related cancers include colorectal, endometrial, gastric, ovarian, pancreas, ureter and renal pelvis, brain (usually glioblastoma), biliary tract, small intestinal cancers, in addition to sebaceous carcinomas and keratoacanthomas in Muir-Torre syndrome.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-related cancer.

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

The right time is different for every 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.

Upon receipt of a fully completed order, our team will verify coverage with your patient’s healthcare insurance plan and estimate their likely out-of-pocket responsibility. If your patient’s estimated responsibility is over $100, we will notify you and/or your patient prior to test initiation to discuss options for continuation or cancellation of the test. Please note that orders lacking complete information will not be processed.

On average, results will be completed 14 to 21 days after receipt of the sample in the laboratory if the family history form and order are complete and the health plan does not require preauthorization. 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 detected in the PMS2 gene and a diagnosis of Lynch syndrome. A positive result does not mean that an individual has a diagnosis of cancer. Pathogenic and likely pathogenic variants in PMS2 have an autosomal dominant pattern of inheritance, meaning that first-degree relatives have a 50% chance of having the same result. Rarely, if an individual inherits two different mutations (one from each parent) in PMS2, then they have a diagnosis of autosomal recessive constitutional mismatch repair deficiency (CMMRD).¹ Specific risk information will be provided in the result report, and you can visit our website at QuestHereditaryCancer.com for more information.

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 the PMS2 gene. 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 genetic counselor.

Individual without previously diagnosed cancer but with a family history of cancer: An individual’s risk of tumors or cancer is based on their personal and family histories. Testing an affected family member may further inform this risk assessment. 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 genetic counselor.

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. If you have questions, please call Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463) to speak with a genetic counselor.