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Lynch Syndrome via the EPCAM Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7143 EPCAM 81479 81479,81403 $540 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7143EPCAM81479 81403(x1), 81479(x1) $540 Order Options and Pricing

Pricing Comments

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.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Hannah Cox, PhD

Clinical Features and Genetics

Clinical Features

Lynch Syndrome, also called Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is an inherited cancer syndrome mainly caused by germline mutations in DNA mismatch repair (MMR) genes. MMR genes are responsible for repairing small sequence errors, or mismatches, during DNA replication. Mutations in certain single mismatch repair genes can cause widespread genomic instability characterized by the expansion or contraction of short tandem repeat sequences, or microsatellites (Grady and Carethers 2008). This phenomenon of microsatellite instability (MSI) leads to somatic mutations in oncogenes and/or tumor suppressor genes, including TGFβIIR and NF1 among others (Wang et al. 2003). As a result, Lynch Syndrome is marked by early onset and 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). 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 pathological MSI within tumors (Vasen et al. 1999).

Genetics

Lynch Syndrome is an autosomal dominant disease caused mainly by germline mutations in one of four MMR genes: MLH1, MSH2, MSH6, and PMS2 (Peltomäki and Vasen 2004; Kohlmann and Gruber. 2012). Mutations in the MLH1 and MSH2 genes account for 80-90% of all Lynch patients and most frequently occur in families meeting the stringent Amsterdam I criteria. Mutations in MSH6 and PMS2 account for most of the remaining Lynch patients and are often found in families with atypical HPNCC symptoms, such as low rates of MSI and/or extracolonic carcinomas. Mutations 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 mutations in the EPCAM cause inactivation of MSH2 via hypermethylation in approximately 1-3% of individuals with Lynch Syndrome (Kohlmann and Gruber. 2012). The only reported mutations of the EPCAM gene that are causative for Lynch Syndrome are large deletions. Missense, nonsense and splicing mutations are involved in congenital tufting enteropathy (Human Gene Mutation Database). 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).

Clinical Sensitivity - Sequencing with CNV PG-Select

The clinical sensitivity of EPCAM sequence variants in Lynch syndrome is unknown as no sequence variants have been reported for this disease; however sequence variants in the EPCAM gene are known to be causative for congenital tufting enteropathy. The clinical sensitivity of EPCAM deletions is 1-3% of individuals with Lynch Syndrome (Kohlmann and Gruber 2012).

Testing Strategy

This test provides full coverage of all coding exons of the EPCAM gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with a Lynch Syndrome or congenital tufting enteropathy diagnosis, and relatives of patients who have a verified EPCAM mutation. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

Gene

Official Gene Symbol OMIM ID
EPCAM 185535
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Colorectal Cancer Predisposition via the POLD1 Gene
Colorectal Cancer Predisposition via the POLE Gene
Hereditary Breast and Ovarian Cancer - High Risk and Lynch Syndrome Panel
Hereditary Endometrial Cancer Panel
Lynch Syndrome via the MLH1 Gene
Lynch Syndrome via the PMS2 Gene
Lynch Syndrome via MSH6 Gene

Citations

  • Grady WM, Carethers JM. 2008. Genomic and Epigenetic Instability in Colorectal Cancer Pathogenesis. Gastroenterology 135: 1079–1099. PubMed ID: 18773902
  • Human Gene Mutation Database (Bio-base).
  • Jang E, Chung DC. 2010. Hereditary Colon Cancer: Lynch Syndrome. Gut and Liver 4: 151. PubMed ID: 20559516
  • Kempers MJ, Kuiper RP, Ockeloen CW, Chappuis PO, Hutter P, Rahner N, Schackert HK, Steinke V, Holinski-Feder E, Morak M, Kloor M, Büttner R, et al. 2011. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. The Lancet Oncology 12: 49–55. PubMed ID: 21145788
  • Kohlmann W, Gruber SB. 2012. Lynch Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301390
  • Peltomäki P, Vasen H. 2004. Mutations associated with HNPCC predisposition–Update of ICG-HNPCC/INSiGHT mutation database. Disease markers 20: 269–276. PubMed ID: 15528792
  • Vasen HF, Watson P, Mecklin J-P, Lynch HT. 1999. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 116: 1453–1456. PubMed ID: 10348829
  • Wang Q, Montmain G, Ruano E, Upadhyaya M, Dudley S, Liskay MR, Thibodeau SN, Puisieux A. 2003. Neurofibromatosis type 1 gene as a mutational target in a mismatch repair-deficient cell type. Human genetics 112: 117–123. PubMed ID: 12522551

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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 Method (Backbone)


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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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