Invitae Familial Adenomatous Polyposis Test

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  • Test code: 01709
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Test description

This test analyzes the APC gene. Pathogenic variants in this gene can cause APC-associated polyposis conditions, which include familial adenomatous polyposis (FAP) and three FAP subtypes: attenuated FAP (AFAP), Gardner syndrome, and Turcot syndrome. These disorders are primarily associated with the development of numerous colon polyps and colon cancer.

Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (1 gene)

Alternative tests to consider

APC can also be ordered as part of a broader panel to test for different types of hereditary cancer, including colorectal and pancreatic cancers. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.

  • APC-associated polyposis conditions
    • familial adenomatous polyposis (FAP)
      • attenuated familial adenomatous polyposis
    • Gardner syndrome
    • Turcot syndrome

Familial adenomatous polyposis (FAP) is a colorectal cancer syndrome characterized by the development of hundreds to thousands of precancerous (adenomatous) polyps, typically beginning in adolescence or early adulthood. Without a prophylactic colectomy, individuals with FAP have a lifetime risk of almost 100% of developing colorectal cancer. One specific pathognomonic finding is congenital hyperplasia of the retinal pigment epithelium (CHRPE), which requires a specialized eye examination to identify.

FAP has three subtypes: Gardner syndrome, Turcot syndrome, and attenuated FAP (AFAP). Gardner syndrome has the same disease progression and risk of colon cancer as classic FAP but is also associated with the development of other extracolonic findings, both benign and malignant. These include desmoid tumors, sebaceous cysts, osteomas, supernumerary teeth, and cancer of the duodenum, exocrine pancreas, thyroid (papillary adenocarcinoma), liver (hepatoblastomas), and central nervous system (medulloblastomas). Turcot syndrome presents with numerous colon adenomas and medulloblastomas.AFAP has a later age of onset than classic FAP, presents with fewer adenomatous polyps (<100), and has an overall lower lifetime risk of developing cancer (approximately 70%).

FAP is a highly penetrant condition. If it is left untreated, affected individuals have a lifetime risk of nearly 100% of developing colorectal cancer. For AFAP, the lifetime risk for colorectal cancer is 70%. See the table below for specific cancer risks:

Cancer typeCancer risk
ColonUp to 100% (70% for attenuated FAP)
Duodenal4%-12%
Thyroid1%-2%
Brain1%-2%
Hepatoblastoma (up to age 5)1%-2%
GastricUp to 0.5%
PancreaticElevated

Analysis of the APC gene detects pathogenic variants in up to 90% of individuals with clinical FAP.

FAP is inherited in an autosomal dominant pattern. Most cases are inherited from a parent; however, up to 25% of cases are due to a spontaneous de novo mutation.

APC-associated polyposis conditions historically accounted for approximately 0.5% of all colorectal cancer, but this number is decreasing with increased awareness, early detection, and intervention. Collectively, the APC-associated polyposis conditions have a prevalence of approximately 2-3 in 100,000 individuals.

A clinical diagnosis of FAP is established if an individual has at least one of the following:

  • at least 100 colorectal adenomatous polyps
  • fewer than 100 adenomatous polyps and a relative with FAP

A clinical diagnosis of attenuated FAP (AFAP) should be considered if an individual has at least one of the following:

  • ten to 99 colonic adenomatous polyps
  • a personal history of colorectal cancer before age 60 years and a family history of multiple adenomatous polyps

For additional details, see the clinical criteria for FAP and AFAP established by the National Comprehensive Cancer Network:

  1. American Society of Clinical Oncology, Cancer.Net: Familial Adenomatous Polyposis. http://www.cancer.net/cancer-types/familial-adenomatous-polyposis Accessed September 2015.
  2. Bianchi, LK, et al. Fundic gland polyp dysplasia is common in familial adenomatous polyposis. Clin. Gastroenterol. Hepatol. 2008; 6(2):180-5. doi: 10.1016/j.cgh.2007.11.018. PMID: 18237868
  3. Biasco, G, et al. Risk of duodenal cancer in patients with familial adenomatous polyposis. Gut. 2004; 53(10):1547; author reply 1547. doi: 10.1136/gut.2003.027771. http://ncbi.nlm.nih.gov/pubmed/15361514 PMID: 15361514
  4. Giardiello, FM, et al. Hepatoblastoma and APC gene mutation in familial adenomatous polyposis. Gut. 1996; 39(6):867-9. doi: 10.1136/gut.39.6.867. http://ncbi.nlm.nih.gov/pubmed/9038672 PMID: 9038672
  5. Giardiello, FM, et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut. 1993; 34(10):1394-6. doi: 10.1136/gut.34.10.1394. PMID: 8244108
  6. Giardiello, FM, et al. The use and interpretation of commercial APC gene testing for familial adenomatous polyposis. N. Engl. J. Med. 1997; 336(12):823-7. doi: 10.1056/NEJM199703203361202. PMID: 9062090
  7. Groen, EJ, et al. Extra-intestinal manifestations of familial adenomatous polyposis. Ann. Surg. Oncol. 2008; 15(9):2439-50. doi: 10.1245/s10434-008-9981-3. PMID: 18612695
  8. Groves, CJ, et al. Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study. Gut. 2002; 50(5):636-41. doi: 10.1136/gut.50.5.636. http://ncbi.nlm.nih.gov/pubmed/11950808 PMID: 11950808
  9. Gurbuz, AK, et al. Desmoid tumours in familial adenomatous polyposis. Gut. 1994; 35(3):377-81. doi: 10.1016/0959-8049(94)90655-6. PMID: 8150351
  10. Half, E, et al. Familial adenomatous polyposis. Orphanet J Rare Dis. 2009; 4:22. doi: 10.1186/1750-1172-4-22. PMID: 19822006
  11. Hamilton, SR, et al. The molecular basis of Turcot's syndrome. N. Engl. J. Med. 1995; 332(13):839-47. doi: 10.1056/NEJM199503303321302. http://ncbi.nlm.nih.gov/pubmed/7661930 PMID: 7661930
  12. Hampel, H, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet. Med. 2015; 17(1):70-87. doi: 10.1038/gim.2014.147. PMID: 25394175
  13. Harach, HR, et al. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology. 1994; 25(6):549-61. PMID: 7698732
  14. Harach, HR, et al. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology. 1994; 25(6):549-61. doi: 10.1111/j.1365-2559.1994.tb01374.x. http://ncbi.nlm.nih.gov/pubmed/7698732
  15. Hughes, LJ, Michels, VV. Risk of hepatoblastoma in familial adenomatous polyposis. Am. J. Med. Genet. 1992; 43(6):1023-5. PMID: 1329510
  16. Hughes, LJ, Michels, VV. Risk of hepatoblastoma in familial adenomatous polyposis. Am. J. Med. Genet. 1992; 43(6):1023-5. doi: 10.1002/ajmg.1320430621. http://ncbi.nlm.nih.gov/pubmed/1329510
  17. Jasperson, KW, Burt, RW. APC-Associated Polyposis Conditions. 1998 Dec 18. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301519
  18. Latchford, AR, et al. A 10-year review of surgery for desmoid disease associated with familial adenomatous polyposis. Br J Surg. 2006; 93(10):1258-64. PMID: 16952208
  19. Leoz, ML, et al. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. Appl Clin Genet. 2015; 8:95-107. doi: 10.2147/TACG.S51484. PMID: 25931827
  20. National Comprehensive Cancer Network®, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Colorectal. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed September 2015.
  21. National Library of Medicine, Genetics Home Reference: Familial Adenomatous Polyposis. http://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis Accessed September 2015.
  22. Neklason, DW, et al. American founder mutation for attenuated familial adenomatous polyposis. Clin. Gastroenterol. Hepatol. 2008; 6(1):46-52. PMID: 18063416
  23. Petersen, GM, et al. Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage. Gastroenterology. 1991; 100(6):1658-64. PMID: 1673441
  24. Plail, RO, et al. Adenomatous polyposis: an association with carcinoma of the thyroid. Br J Surg. 1987; 74(5):377-80. PMID: 3036290
  25. Plail, RO, et al. Adenomatous polyposis: an association with carcinoma of the thyroid. Br J Surg. 1987; 74(5):377-80. doi: 10.1002/bjs.1800740517. http://ncbi.nlm.nih.gov/pubmed/3036290
  26. Spigelman, AD, et al. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989; 2(8666):783-5. doi: 10.1016/s0140-6736(89)90840-4. PMID: 2571019
  27. Spirio, L, et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell. 1993; 75(5):951-7. doi: 10.1016/0092-8674(93)90538-2. PMID: 8252630

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
APC* NM_000038.5

APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis.