Lynch syndrome (also known as Hereditary Non-Polyposis Colon Cancer, HNPCC), is an autosomal dominant hereditary cancer syndrome that accounts for 3-5% of all colon cancers.   Lynch syndrome-associated tumors are characterized by microsatellite instability (MSI) and are caused by germline mutations in any of four mismatch repair (MMR) genes (MLH1, MSH6, MSH2, PMS2).  The risk of colon and gastric cancers are increased in both sexes, and women with Lynch syndrome have an increased risk for endometrial and ovarian cancers.  

The testing strategy for Lynch syndrome includes screening by MSI analysis followed by immunohistochemistry (IHC) testing of MMR proteins.   Full gene sequencing can then be performed to identify germline mutations in the putative mutated gene(s) identified by IHC.   (Please contact Client Services at (855) 535-1522 for more information regarding MSI and IHC testing).  Germline mutations in MLH1 and MSH2 account for 90% of Lynch syndrome cases while mutations of MSH6 and PMS2 comprise the remaining fractions.  While one study indicated that 65% of MSH2 and 87% of MLH1 variants were point mutations (the rest being gross deletions/duplications), comprehensive clinical sensitivity of MSH2, MLH1, and MSH6 sequencing is unknown.  

Reasons for Referral:

  • Unknown familial mutation in MMR gene(s) with a positive family history of colorectal cancer without IHC and/or MSI information
  • Identification of inherited genetic defects in MMR gene(s) in colorectal cancer patients with tumors
  • testing positive by IHC and/or MSI
  • Predispositional testing for asymptomatic family members with a positive family history of colorectal cancer


This test has 2 components:
Component 1: Sequencing for MLH1, MSH2, MSH6 is carried out by amplification of all 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.

Component 2: Deletion/Duplication analysis is performed using a customized “CytoSUre “exon-centric” array (Oxford Gene Technology).  The targeted array has enhanced probes targeted to the exonic regions of MLH1, MSH2, and MSH6.  The arrays will be run using Agilent SureScan technology.

Specimen Requirements:

Blood:  EDTA or ACD (Solution A or B)

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

DNA: 10µg at a minimum of 100ng/µL

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

Test Performed (Days):


Turn Around Time:

14 – 21 days

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Please use the cold pack provided in the KDL shipping kit.
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping materials and procedures at (855) 535-1522.


  1. Balmaña J, Stockwell DH, Steyerberg EW, et al. Prediction of MLH1 and MSH2 Mutations in Lynch Syndrome. JAMA: The Journal of the American Medical Association. 2006;296(12):1469 -1478.
  2. Bonadona, V. et al., 2011. Cancer Risks Associated With Germline Mutations in MLH1, MSH2, and MSH6   Genes in Lynch Syndrome. JAMA: The Journal of the American Medical Association, 305(22), pp.2304-2310.
  3. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group, 2009.  Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genetics in Medicine, 11(1), pp.35-41.
  4. Goodfellow, P.J. et al., 2003. Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers. Proceedings of the National Academy of Sciences, 100(10), pp.5908-5913.

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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