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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
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Invitae Familial Adenomatous Polyposis Test

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), attenuated FAP (AFAP), and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). 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.

  • Familial adenomatous polyposis (FAP)
  • Attenuated familial adenomatous polyposis (AFAP)
  • Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS)

Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition 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 nearly 100% for developing colorectal cancer. 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%).

GAPPS is characterized by fundic gland polyposis and an increased risk of gastric cancer (gastric adenocarcinoma). Polyps are often associated with low-grade and focally high-grade dysplasia. Unlike other pathogenic variants in APC, the risk of colorectal polyposis and cancer appears to be lower. GAPPS is caused by pathogenic variants in promoter 1B of the APC gene, which this test analyzes.

FAP was previously divided into subtypes including Turcot and Gardner syndromes. These subtypes were defined by the presence of certain extracolonic findings such as desmoid tumors, sebaceous cysts, osteomas, supernumerary teeth, and cancers of the duodenum, exocrine pancreas, thyroid (papillary adenocarcinoma), liver (hepatoblastomas), and central nervous system (medulloblastomas). It is now recognized that these subtypes are part of the clinical spectrum of APC-associated polyposis conditions.

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%. GAPPS-associated cancer risks are currently unknown. See the table below for FAP-associated cancer risks:

Cancer typeCancer risk
ColonUp to 100% (70% for attenuated FAP)
SarcomaUp to 25%
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. The clinical sensitivity for GAPPS is currently uncertain.

APC-associated polyposis conditions are 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.

Clinical testing for FAP should be considered in individuals with:

  • 10 or more adenomatous colon polyps with or without a colorectal or other FAP-associated cancer
  • cribriform morular variant of papillary thyroid cancer
  • a desmoid tumor
  • hepatoblastoma diagnosed before the age of 5

Clinical testing for GAPPS should be considered in individuals with:

  • gastric polyps
  • fundic gland polyps
  • >100 polyps in the proximal stomach, or more than 30 polyps in a first-degree relative of an individual with GAPPS
  • relative with gastric polyps, fundic gland polyps or gastric adenocarcinoma

  1. 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
  2. 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
  3. 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
  4. Petersen, GM, et al. Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage. Gastroenterology. 1991; 100(6):1658-64. PMID: 1673441
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  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. 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
  12. 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
  13. 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
  14. 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
  15. Plail, RO, et al. Adenomatous polyposis: an association with carcinoma of the thyroid. Br J Surg. 1987; 74(5):377-80. PMID: 3036290
  16. 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
  17. 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
  18. Hughes, LJ, Michels, VV. Risk of hepatoblastoma in familial adenomatous polyposis. Am. J. Med. Genet. 1992; 43(6):1023-5. PMID: 1329510
  19. 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
  20. 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
  21. National Library of Medicine, Genetics Home Reference: Familial Adenomatous Polyposis. http://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis Accessed February 2018.
  22. American Society of Clinical Oncology, Cancer.Net: Familial Adenomatous Polyposis. http://www.cancer.net/cancer-types/familial-adenomatous-polyposis Accessed February 2018.
  23. 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 February 2018.
  24. Li, J, et al. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant. Am. J. Hum. Genet. 2016; 98(5):830-42. PMID: 27087319
  25. Liang, J, et al. APC polymorphisms and the risk of colorectal neoplasia: a HuGE review and meta-analysis. Am. J. Epidemiol. 2013; 177(11):1169-79. PMID: 23576677
  26. Robson, ME, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J. Clin. Oncol. 2010; 28(5):893-901. PMID: 20065170
  27. Sieber, OM, et al. Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation. Gut. 2006; 55(10):1440-8. PMID: 16461775
  28. Burt, RW, et al. Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis. Gastroenterology. 2004; 127(2):444-51. PMID: 15300576
  29. Laken, SJ, et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nat. Genet. 1997; 17(1):79-83. PMID: 9288102
  30. van, der, Luijt, RB, et al. APC mutation in the alternatively spliced region of exon 9 associated with late onset familial adenomatous polyposis. Hum. Genet. 1995; 96(6):705-10. PMID: 8522331
  31. Bisgaard, ML, et al. Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Hum. Mutat. 1994; 3(2):121-5. PMID: 8199592
  32. Repak, R, et al. The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature. Gastrointest. Endosc. 2016; 84(4):718-25. PMID: 27343414
  33. Syngal, S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am. J. Gastroenterol. 2015; 110(2):223-62; quiz 263. doi: 10.1038/ajg.2014.435. PMID: 25645574
  34. Worthley, DL, et al. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome. Gut. 2012; 61(5):774-9. PMID: 21813476
  35. Pollock, J, Welsh, JS. Clinical cancer genetics: Part I: Gastrointestinal. Am. J. Clin. Oncol. 2011; 34(3):332-6. doi: 10.1097/COC.0b013e3181dea432. PMID: 20859198
  36. Rohlin, A, et al. Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis. Oncogene. 2011; 30(50):4977-89. PMID: 21643010
  37. Snow, AK, et al. APC promoter 1B deletion in seven American families with familial adenomatous polyposis. Clin. Genet. 2015; 88(4):360-5. PMID: 25243319
  38. Lin, Y, et al. Novel APC promoter and exon 1B deletion and allelic silencing in three mutation-negative classic familial adenomatous polyposis families. Genome Med. 2015; 7(1):42. PMID: 25941542
  39. Kadiyska, TK, et al. APC promoter 1B deletion in familial polyposis--implications for mutation-negative families. Clin. Genet. 2014; 85(5):452-7. PMID: 23725351
  40. Pavicic, W, et al. Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis. Genes Chromosomes Cancer. 2014; 53(10):857-64. PMID: 24946964
  41. Neklason, DW, et al. American founder mutation for attenuated familial adenomatous polyposis. Clin. Gastroenterol. Hepatol. 2008; 6(1):46-52. PMID: 18063416

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 in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

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.