Download Colon Cancer Panel

ApolloGen, Inc.
13766 Alton Parkway
Suite 147
Irvine CA 92618
Phone: (949) 916-8886
Fax: (949) 916-8899
[email protected]
www.apollogen.com
Colon Cancer Panel
Next Gen Sequencing Test Specifications
Disease Overview
Approximately 5%, or 1 in 20, Americans will be diagnosed with cancer of the colon or rectum in their
lifetime. Colorectal cancer is the fourth most common type of cancer in men and women. In the United
States, estimately 134,490 new cases of colon and rectum cancer were diagnosed in 2016.
Colorectal cancer (CRC) often begins as a growth called a polyp, which may form on the inner wall of the
colon or rectum. Some polyps become cancerous over time. Finding polyps early with screening tests, and
removing them promptly can prevent colorectal cancer. The main risk factors of colorectal cancer are aging,
chronic inflammatory bowel disease, a personal or family history of colorectal cancer or colorectal polyps,
and a genetic syndrome, such as Lynch syndrome.
In general, people who are at risk of having inherited colorectal cancer and who could benefit from genetic
testing may have one or more of the following red flags within their personal or family history:
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a strong family history of colorectal cancer and/or polyps
multiple primary cancers in a patient with colorectal cancer
several family members with colorectal cancer and/or other cancers associated with inherited
cancer syndrome, such as endometrial cancer
early age at diagnosis of colorectal cancer
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ApolloGen’s Colon Cancer Panel analyzes 12 critical high-risk genes that have been associated with
colorectal cancer. It also covers the most common and well-described hereditary colorectal cancer
syndromes, including Lynch syndrome (also referred to as hereditary nonpolyposis colorectal cancer
[HNPCC]), Familial Adenomatous Polyposis, Juvenile Polyposis syndrome, Cowden syndrome, Peutz-Jegher
syndrome, MUTYH-associated polyposis, etc.
Recent studies have convincingly demonstrated that hereditary and sporadic tumors may indeed require
distinct treatment approaches. Genetic testing facilitates the identification of hereditary colon cancer
syndromes, alerts the patient about risks of having other cancers, empowers patients to make their medical
decisions and provides information for other at-risk family members. A molecular diagnosis of inherited
colorectal syndrome will determine the most appropriate medical management recommendation for the
patient. Colonoscopy for CRC screening and surveillance is performed much earlier and more frequently in
individuals who may be predisposed to developing hereditary colorectal cancer syndromes; and has been
associated with improved survival outcomes. In addition, extracolonic surveillance for other associated
cancers is also important and strongly recommended once the diagnosis of a hereditary colorectal cancer
syndrome has been established. In some types of inherited colon cancer syndrome, prophylactic surgery
(colectomy) has also been shown to significantly improve survival of affected patients. Furthermore,
sometimes the knowledge of genetic mutation status may qualify patients for gene-specific clinical trials
and research studies as well.
Indications for Testing
1. Confirmation of diagnosis in patients with personal or family history suggestive of a predisposition to
hereditary colorectal cancer syndromes.
2. Determine the most appropriate clinical management recommendations.
3. Assessment for at-risk family members.
Requisition Form: Cancer Test Requisition Form or General Test Requisition Form (www.apollogen.com)
Genes (12): APC, BMPR1A, CDH1, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53
CPT Codes: 81201×1, 81292×1, 81295×1, 81298×1, 81317×1, 81321×1, 81405×2, 81406×3, 81479×1
Turnaround Time: 4 weeks
Specimen Requirement: 3-5 mL Blood (EDTA) – Lavender Top Tube (preferred);
Saliva samples are optional
Other Specimen Types: Contact ApolloGen Diagnostic Laboratory
Pricing: Please contact us at (949) 916-8886 or at [email protected] for current pricing
Testing Methodology
Genomic DNA is extracted from the patient’s specimen and fragmented via sonication. All of the exons,
flanking intronic (at least 10 nucleotides into the introns), and untranslated regions (5’ and 3’) of the
targeted genes are enriched using capture-based hybridization. Massively parallel sequencing is applied to
the enriched target DNA regions to detect mutations. Variants with an allele frequency > 1% are considered
likely benign polymorphisms, and are not included in the final report. Interpretation of rare alterations with
allele frequency <1% is based on ACMG guidelines. All pathogenic and likely pathogenic variants are verified
by Sanger Sequencing.
Massively parallel sequencing can reliably detect insertion/deletion mutations smaller than 10 base pairs.
However, larger insertion, deletion, duplication due to rearrangement, and mutations in regulatory and
deep intronic regions cannot be detected by this technology. Rare primer site variants may lead to
erroneous results that may need further investigation.
Analytical Sensitivity:
This test can detect >95% of the small variants in the examined regions. Please contact us for detailed
information regarding coverage for specific genes of interest.
Related Test
iGene Cancer Panel
Simultaneously analyzes 20 critical genes associated with an increased risk for breast, ovarian, endometrial,
colorectal, pancreatic and other cancers.
Breast Cancer Panel
Analyzes 19 established genes that are associated with an increased risk of breast cancer.
Variant Classification
Sequencing results will be interpreted and reported following the recommendations of the American
College of Medical Genetics (www.acmg.net). Sequence variations will be analyzed and classified into the
following categories based on current scientific knowledge. Variants found in categories 1-3 (pathogenic,
likely pathogenic, and variants of unknown clinical significance) will be reported.
1.
2.
3.
4.
5.
Pathogenic: Pathogenic variants include nonsense mutations and frame shift mutations that are predicted
to result in premature protein truncation, splice site mutations, and previously reported missense
mutations that are recognized as disease-causing by databases and the scientific literature.
Likely Pathogenic: Likely pathogenic variants are those variants that are likely to adversely affect gene
function, but for which there is no conclusive evidence to strongly support pathogenicity.
Variant of Unknown Clinical Significance (VUS): VUSs are sequence variations for which there is insufficient
evidence to either confirm or exclude pathogenicity.
Likely Benign: Likely benign variants are sequence variations for which there is significant, but not
conclusive evidence supporting that the variant is not disease-causing.
Negative: A negative classification is reported when no disease-causing variant is found, or a variant is
classified as a benign variant based on the ACMG criteria, the population data, or if there is no clinical
significance based on review of the literature and mutation databases.
References
1. Colorectal (Colon) Cancer, https://www.cdc.gov/cancer/colorectal/index.htm, Disease Control and
Prevention.
2. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J,
Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review,
1975-2013, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2013/, based on
November 2015 SEER data submission, posted to the SEER web site, April 2016.
3. National Cancer Institute at the National Institutes of Health. Colorectal Cancer – Health Professional
version. https://www.cancer.gov/types/colorectal/hp
4. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology, Colorectal Cancer
Screening (Version 2.2016).
https://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening. Accessed February, 2017
5. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology, Gastric Cancer
(Version 3. 2016). https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. Accessed
January, 2017
6. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology, Genetic/Familial
High‐Risk Assessment: Colorectal (Version 2.2016).
https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf. Accessed January, 2017
7. Jasperson, K. W. Genetic testing by cancer site: colon (polyposis syndromes). Cancer J 18, 328–333
(2012).
8. American Cancer Society. Cancer Facts & Figures 2017. https://www.cancer.org/research/cancer-factsstatistics/all-cancer-facts-figures/cancer-facts-figures-2017.html
9. American Cancer Society. Colorectal Cancer Facts & Figures 2014-2016. Atlanta: American Cancer
Society, 2014. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-andstatistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2014-2016.pdf
10. Jasperson, K. W., Tuohy, T. M., Neklason, D. W. & Burt, R. W. Hereditary and familial colon cancer.
Gastroenterology 138, 2044–2058 (2010).
12. Imyanitov, E. N. & Byrski, T. Systemic treatment for hereditary cancers: a 2012 update. Hered Cancer
Clin Pract 11, 2 (2013).
13. O’Daniel, J. M. & Lee, K. Whole-genome and whole-exome sequencing in hereditary cancer: impact on
genetic testing and counseling. Cancer J 18, 287–292 (2012).
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