Lynch Syndrome Panel

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
5463 EPCAM 81479,81403 Order Options and Pricing
MLH1 81292,81294
MSH2 81295,81297
MSH6 81298,81300
PMS2 81317,81319
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
5463Genes x (5)81479 81292, 81294, 81295, 81297, 81298, 81300, 81317, 81319, 81403, 81479 $540 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available.

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Lynch syndrome, also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is an inherited cancer syndrome mainly caused by germline pathogenic variants in DNA mismatch repair (MMR) genes. MMR genes encode proteins that repair small sequence errors, or mismatches, during DNA replication. Pathogenic variants in mismatch repair genes can cause widespread genomic instability characterized by the expansion and contraction of short tandem repeat sequences (microsatellites) (Grady and Carethers. 2008. PubMed ID: 18773902). As a result, Lynch syndrome is marked by early onset and a high lifetime risk of cancer, particularly in the right colon but also in the endometrium, ovary, stomach, bile duct, kidney, bladder, ureter, and brain (Jang and Chung. 2010. PubMed ID: 20559516). Clinical hallmarks of Lynch Syndrome, as delineated by the Amsterdam criteria, include heritable colorectal (Type I) or extracolonic (Type II) cancer, present in at least three relatives over at least two consecutive generations, with an onset of cancer before the age of 50 in at least one case, and exclusion of familial adenomatous polyposis (FAP) (Vasen et al. 1999. PubMed ID: 10348829).

Genetics

Lynch syndrome is an autosomal dominant disease mainly caused by germline pathogenic variants in one of four MMR genes: MLH1, MSH2, MSH6, and PMS2 (Peltomäki and Vasen. 2004. PubMed ID: 15528792; Kohlmann and Gruber. 2014. PubMed ID: 20301390). Pathogenic variants in the MLH1 and MSH2 genes account for approximately 80-90% of all Lynch syndrome patients, and most frequently occur in families meeting the stringent Amsterdam criteria. Pathogenic variants in the MSH6 and PMS2 genes account for most of the remaining Lynch patients, and are often found in families with atypical HNPCC symptoms, such extracolonic carcinomas; and have also been found to have a low rate of microsatellite instability.

Pathogenic variants in another gene, EPCAM, which encodes a calcium-independent cell adhesion molecule and not a mismatch repair protein, are also involved in Lynch syndrome. Germline pathogenic variants in the EPCAM gene can cause inactivation of the nearby MSH2 gene via hypermethylation in 1-3% of individuals with Lynch syndrome (Kohlmann and Gruber. 2014. PubMed ID: 20301390). The only reported pathogenic variants in the EPCAM gene that are causative for Lynch Syndrome are large deletions (Human Gene Mutation Database; www.insight-group.org). The cumulative incidence of colon cancer risk from EPCAM deletions has been estimated to be 75% by 70 years of age, and for endometrial cancer in women to be 12% (Kempers et al. 2011. PubMed ID: 21145788).

A germline inversion of exons 1-7 in MSH2 has been reported in fourteen individuals from eleven un-related families clinically presenting with Lynch syndrome associated phenotypes including colorectal, endometrial, gastric, and ovarian cancer (Wagner et al. 2002. PubMed ID: 12203789; Rhees et al. 2013. PubMed ID: 24114314; Mork et al. 2016. PubMed ID: 28004223).

See individual gene test descriptions for information on molecular biology of gene products and mutation spectra.

Testing Strategy

This panel typically provides ≥98% coverage of all coding exons of the genes listed, plus ~10 bases of flanking noncoding DNA. We define coverage as ≥20X NGS reads or Sanger sequencing.

This test also includes analysis of the inversion of exons 1-7 in MSH2.

Clinical Sensitivity - Sequencing with CNV PG-Select

Lynch syndrome is attributed to pathogenic sequence variants in the MLH1, MSH2, MSH6, and PMS2 genes in approximately 50%, 40%, 7-10% and <5% of cases, respectively (Kohlmann and Gruber. 2014. PubMed ID: 20301390). The majority of these variants are single nucleotide substitutions or small insertions and deletions. Missense, nonsense and splicing EPCAM pathogenic variants are involved in congenital tufting enteropathy (Human Gene Mutation Database), while EPCAM deletions account for 1-3% of Lynch syndrome cases (Kohlmann and Gruber. 2014. PubMed ID: 20301390). Large deletions and genetic rearrangements account for 20%, 5%, 20%, 7%, and 100% of identifiable pathogenic variants in the MSH2, MLH1, PMS2, MSH6, and EPCAM genes (Kohlmann and Gruber. 2014. PubMed ID: 20301390).

Indications for Test

This test is suitable for individuals with multifocal, recurrent, and early onset (< 50 years) colorectal tumors or a family history of colorectal tumors. Germline pathogenic variants in the Lynch syndrome genes have also been shown to be associated with ovarian cancer (Watson et al. 2008. PubMed ID: 18398828). This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

Genes

Official Gene Symbol OMIM ID
EPCAM 185535
MLH1 120436
MSH2 609309
MSH6 600678
PMS2 600259
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Grady and Carethers. 2008. PubMed ID: 18773902
  • Human Gene Mutation Database (Bio-base).
  • Jang and Chung. 2010. PubMed ID: 20559516
  • Kempers et al. 2011. PubMed ID: 21145788
  • Kohlmann and Gruber. 2014. PubMed ID: 20301390
  • Mork et al. 2016. PubMed ID: 28004223
  • Peltomäki and Vasen. 2004. PubMed ID: 15528792
  • Rhees et al. 2013. PubMed ID: 24114314
  • Vasen et al. 1999. PubMed ID: 10348829
  • Wagner et al. 2002. PubMed ID: 12203789
  • Watson et al. 2008. PubMed ID: 18398828
  • www.insight-group.org

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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