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. Additionally, MLPA or CGH microarray can analyze copy number changes as well. 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: A customized CytoSure “exon-centric” array (Oxford Gene Technology) will be used to detect deletions and duplications. The targeted array has enhanced probes targeted to the exonic regions of PMS2. The arrays are run using Agilent SureScan technology.

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

Saliva: 2 ORAgene Saliva Kit(s) (OGR-500)

Assisted Sailva: 2 ORAgene Assisted Saliva Kit(s) (OGR-575)

Skin Fibroblast: Punch Biopsy, or 2 T-25 confluent flasks

DNA: 10µg at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

For routine testing of blood and saliva (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion. For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

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:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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