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HelpTest Code CRCGP Hereditary Gastrointestinal Cancer Panel, Varies
Ordering Guidance
Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. For more information see FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Necessary Information
Prior Authorization is available, but not required, for this test. If proceeding with the prior authorization process, submit the required form with the specimen.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 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 whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file.
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
2. Molecular Genetics: Inherited Cancer Syndromes Patient Information Sheet (T519)
3. Hereditary Gastrointestinal Cancer Panel Prior Authorization Ordering Instructions
4. If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.
Secondary ID
614571Useful For
Evaluating patients with a personal or family history suggestive of a hereditary gastrointestinal cancer or hereditary polyposis syndrome
Establishing a diagnosis of a hereditary gastrointestinal cancer syndrome or hereditary polyposis syndrome allowing for targeted cancer surveillance based on associated risks
Identifying genetic variants associated with increased risk for gastrointestinal cancer and polyposis, allowing for predictive testing and appropriate screening of at-risk family members
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 26 genes associated with hereditary colorectal cancer, gastric cancer, or polyposis risk: APC (including promoters 1A and 1B), ATM, AXIN2, BMPR1A, CDH1, CHEK2, CTNNA1, EPCAM (copy number variants only), GREM1 (upstream enhancer region duplication only), KIT, MLH1, MLH3, MSH2, MSH3, MSH6, MUTYH, NTHL1, PDGFRA, PMS2, POLD1, POLE, PTEN (including promoter), RNF43, SMAD4, STK11, TP53. For more information, see Method Description and Targeted Genes and Methodology Details for Hereditary Gastrointestinal Cancer Panel.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for hereditary gastrointestinal cancer syndromes and hereditary polyposis syndromes.
Prior Authorization is available for this assay.
Disease States
- Lynch syndrome
Testing Algorithm
First-tier testing may be considered/recommended. For more information see Lynch Syndrome Testing Algorithm.
Special Instructions
- Molecular Genetics: Inherited Cancer Syndromes Patient Information
- Informed Consent for Genetic Testing
- Hereditary Gastrointestinal Cancer Panel Prior Authorization Ordering Instructions
- Lynch Syndrome Testing Algorithm
- Informed Consent for Genetic Testing (Spanish)
- Targeted Genes and Methodology Details for Hereditary Gastrointestinal Cancer Panel
Method Name
Sequence Capture and Next-Generation Sequencing (NGS), Polymerase Chain Reaction (PCR), Sanger Sequencing and/or Multiplex Ligation-Dependent Probe Amplification (MLPA)
Reporting Name
Hereditary GI Cancer PanelSpecimen Type
VariesSpecimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Colorectal cancer occurs in approximately 4% to 6% of individuals in the general population.(1) In some cases, individuals with a personal or family history of colorectal cancer, gastric cancer, or polyposis may be at increased risk of cancer due to a hereditary cancer syndrome.(2,3) Evaluation of the genes on this panel may be useful for families with a history of colorectal cancer, gastric cancer, polyposis, or gastrointestinal cancers to determine cancer risk, surveillance recommendations, and targeted treatments.(2-4)
The most common hereditary colon cancer syndrome is Lynch syndrome, accounting for about 2% to 4% of all colon cancer cases.(2) Lynch syndrome is associated with germline variants in the mismatch repair genes, MLH1, MSH2, MSH6, PMS2, or deletions of the EPCAM gene.(2,3) It is predominantly characterized by significantly increased risks for colorectal and endometrial cancer.(2,3) The lifetime risk for colorectal cancer is highly variable and dependent on the gene involved.(2,3) Other malignancies within the tumor spectrum include gastric cancer, ovarian cancer, hepatobiliary and upper tract urothelial carcinomas, and small bowel cancer.(2,3)
Although rare, individuals and families with polyposis may also be at risk for a hereditary polyposis syndrome, such as familial adenomatous polyposis (FAP).(2) FAP is caused by variants in the APC gene and characterized by numerous adenomatous polyps.(2) The presence of extracolonic manifestations is variable and includes gastric and duodenal polyps, ampullary polyps, osteomas, dental abnormalities (unerupted teeth), congenital hypertrophy of the retinal pigment epithelium (CHRPE), benign cutaneous lesions, desmoid tumors, hepatoblastoma, and extracolonic cancers.(2)
Other genes are also known to cause to hereditary colorectal cancer, gastric cancer, polyposis, and gastrointestinal cancers.(2) The risk for developing cancer associated with these syndromes varies.(2) Some individuals with a disease-causing variant in one of these genes develop multiple primary cancers.(2)
The National Comprehensive Cancer Network and the American Cancer Society provide recommendations regarding the medical management of individuals with hereditary gastrointestinal cancer syndromes.(2,4)
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(5) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Cautions
Clinical Correlations:
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.
To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact the Mayo Clinic Laboratories genetic counselors at 800-533-1710.
Technical Limitations:
Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.
There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.
This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.
Deletion/Duplication Analysis:
This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.
This test is not designed to detect low levels of mosaicism or differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.
Genes may be added or removed based on updated clinical relevance. For the most up to date list of genes included in this test, see Targeted Genes and Methodology Details for Hereditary Gastrointestinal Cancer Panel. For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.
If the patient has had an allogeneic hematopoietic stem cell transplant or a recent blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reclassification of Variants Policy:
Currently, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time.
Variant Evaluation:
Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(5) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.
Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgement.
Clinical Reference
1. Howlader N, Noone AM, Krapcho M, et al: SEER Cancer Statistics Review. 1975-2018. National Cancer Institute; Updated April 2021. Accessed November 8, 2022. Available at: https://seer.cancer.gov/csr/1975_2018/
2. Gupta S, Provenzale D, Llor X, et al: NCCN Guidelines Insights: Genetic/familial high-risk assessment: colorectal, version 2.2019. J Natl Compr Canc Netw. 2019 Sep 1;17(9):1032-1041
3. Idos G, Valle L: Lynch syndrome. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2004. Updated February 2, 2021. Accessed November 8, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1211/
4. Smith RA, Andrews KS, Brooks D, et al: Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin. 2019 May;69(3):184-210
5. 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
Method Description
Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS, multiplex ligation-dependent probe amplification (MLPA), and/or a polymerase chain reaction (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed. PCR and gel electrophoresis is performed to test for the presence of the 10 megabase inversion of coding exons 1-7 of the MSH2 gene.
There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. For details regarding the targeted genes analyzed and specific gene regions not routinely covered, see Targeted Genes and Methodology Details for Hereditary Gastrointestinal Cancer Panel.(Unpublished Mayo method)
Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.
Genes analyzed: APC (including promoters 1A and 1B), ATM, AXIN2, BMPR1A, CDH1, CHEK2, CTNNA1, EPCAM (copy number variants only), GREM1 (upstream enhancer region duplication only), KIT, MLH1, MLH3, MSH2, MSH3, MSH6, MUTYH, NTHL1, PDGFRA, PMS2, POLD1, POLE, PTEN (including promoter), RNF43, SMAD4, STK11, TP53
Day(s) Performed
Varies
Report Available
21 to 28 daysSpecimen Retention Time
Whole Blood: 2 weeks (if available); Extracted DNA: 3 monthsPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81435
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| CRCGP | Hereditary GI Cancer Panel | 97656-3 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 614695 | Test Description | 62364-5 |
| 614696 | Specimen | 31208-2 |
| 614697 | Source | 31208-2 |
| 614698 | Result Summary | 50397-9 |
| 614699 | Result | 82939-0 |
| 614700 | Interpretation | 69047-9 |
| 614701 | Resources | 99622-3 |
| 614702 | Additional Information | 48767-8 |
| 614703 | Method | 85069-3 |
| 614704 | Genes Analyzed | 48018-6 |
| 614705 | Disclaimer | 62364-5 |
| 614706 | Released By | 18771-6 |
Prior Authorization
Insurance preauthorization is available for this testing; forms are available.
Patient financial assistance may be available to those who qualify. Patients who receive a bill from Mayo Clinic Laboratories will receive information on eligibility and how to apply.