• Test Code:
    5051
  • Department:
    Molecular Genetics
  • Test Synonyms:
    Lynch Syndrome SequencingHNPCC
  • CPT Code(s):
    81317
Background:

The protein, Postmeiotic Segregation Increased 2 (PMS2), is a component of the mismatch repair genes. PMS2 interacts with the protein MLH1 and assists correcting DNA replication mistakes. Mutations in this gene have been shown to contribute to about 5% of Hereditary Nonpolyposis Colon cancer, as well as pancreatic and ovarian cancers. PMS2 testing is also recommended upon detection of microsatellite instability (MSI) in tumor tissues due to the possibility deficits in the DNA mismatch repair machinery. This Sanger sequencing test is designed to detect germline variants in all 15 protein coding exons of PMS2. An initial long range PCR step has been designed to ensure any variation detected is not attributed to any of the PMS2 pseudogenes. It is recommended that additional family members to be tested upon detection of a pathogenic variant.

Reasons for Referral:

  • Microsatellite instability detection in tumors
  • Lynch syndrome
  • Colon cancer
  • Pancreatic cancer
  • Ovarian cancer
  • Family history

Methodology:

Sequencing: Sequencing for PMS2 is carried out by performing an initial long range PCR amplification of all 15 exons and intron/exon boundaries followed by bi-directional Sanger sequencing.  The sensitivity of full gene sequencing is estimated to be approximately 99% for single nucleotide substitutions and small insertions/deletions.  All nucleotide changes are analyzed within the context of current databases and literature to predict pathogenicity.

Deletion/Duplication analysis is also available.

Test reporting follows the ACMG Standards & Guidelines for Clinical Genetics Laboratories.

Specimen Requirements:

Blood: EDTA or ACD (Solution A or B):

  • Adult: 5 mL
  • Child: 2-3mL
  • Infant: 1-2mL

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

14-21 days

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

Additional Info: