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Test ID: HCRC Hereditary Colon Cancer Multi-Gene Panel

Useful For

Providing a comprehensive evaluation for hereditary colon cancer in patients with a personal or family history suggestive of a hereditary colon cancer syndrome

 

Serving as a second-tier test for patients in whom previous targeted gene mutation analyses for specific hereditary colorectal cancer-related genes were negative

 

Establishing a diagnosis of a hereditary colon cancer syndrome in some cases, allowing for targeted cancer surveillance of associated extra-colonic organs known to be at increased risk for cancer

 

Identifying mutations within genes known to be associated with increased risk for colon cancer allowing for predictive testing of at-risk family members

Method Name

Custom Sequence Capture and Targeted Next-Generation Sequencing Followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing and Gene Dosage Analysis by Array Comparative Genomic Hybridization (aCGH) or Multiplex Ligation-Dependent Probe Amplification (MLPA)

Reporting Name

Hereditary Colon Cancer Panel

Specimen Type

Varies


Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Necessary Information


 



Specimen Required


Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Additional Information:

1. To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.

2. Prior Authorization is available for this test. Submit the required form with the specimen.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

Colorectal cancer occurs in approximately 5% to 6% of individuals in the general population. In rare cases, individuals with a family history of colorectal cancer may be at increased risk for colon and other cancers due to a single-gene predisposition syndrome, known as hereditary colorectal cancer. The 2 most common hereditary colorectal cancer syndromes are Lynch syndrome and familial adenomatous polyposis (FAP). However, there are multiple other genes that are also known to cause to hereditary colorectal cancer or contribute to an increased risk for colorectal cancer. This panel uses next-generation sequencing (NGS), array comparative genomic hybridization (aCGH), and other technologies to evaluate for germline mutations in 17 genes known to be associated with an increased risk for colon cancer development. Two of the genes listed, CHEK2 and MLH3, are not associated with a known hereditary cancer syndrome defined by a distinct spectrum of tumors. However, literature suggests that mutations in these genes may confer an increased risk for colon cancer and, therefore, are predicted to contribute to cancer risk in patients and families.

 

Gene

Known Association

MLH1

Lynch syndrome

MSH2

Lynch syndrome

MSH6

Lynch syndrome

PMS2

Lynch syndrome

EPCAM

Lynch syndrome

APC

Familial adenomatous polyposis

MYH/MutYH

MYH-associated polyposis

SCG5/GREM1

Hereditary mixed polyposis syndrome

STK11

Peutz-Jeghers syndrome

SMAD4

Juvenile polyposis syndrome

BMPR1A

Juvenile polyposis syndrome

PTEN

PTEN hamartoma tumor syndrome (ie, Cowden syndrome)

CDH1

Hereditary diffuse gastric cancer

AXIN2

Oligodontia-colorectal cancer syndrome

TP53

Li-Fraumeni syndrome

CHEK2

Low-risk gene

MLH3

Low-risk gene

 

Indications for testing include but are not limited to:

-Patients in whom no specific colorectal cancer syndrome is evident but for whom there is a clear familial component

-Patients whose family history is consistent with familial colorectal cancer type X(1)

-Patients with a strong suspicion for a single-gene hereditary colon cancer syndrome based on an autosomal dominant pattern of colon cancer in the family

-Patients with a personal or family history of colonic polyposis

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(2) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Reference

1. Lindor NM, Rabe K, Petersen GM, et al: Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA 2005;293(16):1979-1985

2. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

3. Lindor NM, McMaster ML, Lindor CJ, et al: Concise Handbook of Familial Cancer Susceptibility Syndromes. Second edition. J Natl Cancer Inst Monogr 2008;(38):1-93

4. Genetics of Colorectal Cancer. Edited by JD Potter, NM Lindor. 2009, New York, Springer Verlag, 2009 pp 213-217

5. Jaeger E, Leedham S, Lewis A, et al: Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1. Nat Genet 2012;44(6):699-703

6. Ligtenberg MJL, Kuiper RP, Chan TL, et al: Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet 2009;41(1):112-117

7. Lammi L, Arte S, Somer M, et al: Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 2004;74:1043-1050

8. Liu HX, Zhou XL, Liu T, et al: The role of hMLH3 in familial colorectal cancer. Cancer Res 2003;63(8):1894-1899

Day(s) and Time(s) Performed

Performed weekly, varies

Analytic Time

4 weeks

CPT Code Information

81435

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HCRC Hereditary Colon Cancer Panel In Process

 

Result ID Test Result Name Result LOINC Value
52588 Result Summary 50397-9
52589 Result In Process
52590 Interpretation 69047-9
52591 Additional Information 48767-8
52592 Specimen 31208-2
52593 Source 31208-2
52594 Released By No LOINC Needed

Testing Algorithm

See Colonic Polyposis Syndromes Testing Algorithm in Special Instructions.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

Forms

1. Molecular Genetics: Inherited Cancer Syndromes Patient Information (T519) in Special Instructions

2. Hereditary Colon Cancer Multi-Gene Panel Prior Authorization Ordering Instructions in Special Instructions

3. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

4. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

Oncology Test Request Form (T729) (http://www.mayomedicallaboratories.com/it-mmfiles/oncology-request-form.pdf)

Gastroenterology and Hepatology Test Request Form (T728) (http://www.mayomedicallaboratories.com/it-mmfiles/gastroenterology-and-hepatology-test-request.pdf)

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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