APC Amplified
APC-associated polyposis conditions include Familial
Adenomatous Polyposis (FAP), Gardner syndrome, Turcot
syndrome and attenuated FAP (AFAP).
PrintAPC-associated polyposis conditions include Familial
Adenomatous Polyposis (FAP), Gardner syndrome, Turcot
syndrome and attenuated FAP (AFAP).
Familial Adenomatous Polyposis (FAP) is an autosomal dominant colon cancer predisposition syndrome characterized by hundreds to thousands of adenomatous polyps in the internal lining of the colon and the rectum. It affects 1/8,000 to 1/10,000 individuals and accounts for about 1% of all colorectal cancers. In individuals affected with FAP, colonic polyps generally begin developing at an average age of 16 years. Colon cancer is inevitable without colectomy, and the mean age of colon cancer diagnosis in untreated individuals is 39 years (range 34-43).
Variants of FAP are Gardner syndrome, Turcot syndrome, and attenuated FAP (AFAP).
The Ambry Test: APC AMPLIFIED includes gene sequence analysis with concurrent deletion/duplication analysis of APC. Mutation detection rates are highest in classic FAP and in individuals with a family history of polyposis. Mutations in the APC gene are detectable in up to 88% of individuals affected with classic FAP. The Ambry Test: APC AMPLIFIED is capable of detecting >99% of described mutations in APC.
Familial adenomatous polyposis (FAP) is an autosomal dominant colon cancer predisposition syndrome characterized by hundreds to thousands of adenomatous polyps in the internal lining of the colon and the rectum. It affects 1/8,000 to 1/10,000 individuals and accounts for about 1% of all colorectal cancers.1 In individuals affected with classic FAP, colonic polyps generally begin developing at an average age of 16 years.2 Colon cancer is inevitable without colectomy, and the mean age of colon cancer diagnosis in untreated individuals is age 35-40 years.3
Variants of FAP are Gardner syndrome, Turcot syndrome, and attenuated FAP (AFAP).1 Gardner syndrome is caused by the association of colonic polyposis of classic FAP with osteomas and soft tissue tumors (epidermoid cysts, fibromas, desmoid tumors).4 Turcot syndrome is characterized by colonic polyposis and central nervous system (CNS) tumors, usually medulloblastoma.5 Attenuated FAP (AFAP) is characterized by fewer colonic polyps (<100 polyps), more proximally located polyps, and diagnosis of colon cancer at a later age.6 Other extracolonic manifestations associated with FAP or its variants include polyps of the gastric fundus and duodenum, dental anomalies, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and other associated cancers. Variations in phenotype may relate to the location of the mutation within the APC gene.1
Clinical criteria for typical FAP consist of:
1. One hundred or more colorectal adenomatous polyps*
OR
2. Fewer than 100 adenomatous polyps and a relative with FAP
*NOTE: (1) The diagnosis of FAP is generally considered in individuals with polyposis occurring before age 40 years. (2) The presence of 100 or more colorectal polyps is not specific to FAP; genetic testing of APC may help distinguish FAP from MUTYH-associated polyposis (MAP) or colonic polyposis conditions of unknown etiology.
The predisposition to malignancy is caused by germ-line mutations in the APC gene. Approximately 75-80% of individuals with APC-associated FAP have an affected parent.7 APC is a tumor suppressor gene that regulates several genes involved in the control of cell proliferation and differentiation, cell migration, chromosomal segregation and apoptosis.8 The proposed pathogenic mechanism is that a deleterious mutation in APC causes a loss of defensive cellular mechanisms, thus allowing uncontrolled cellular proliferation and tumor progression. Mutations detected through sequence analysis of the APC gene account for approximately 90% of cases; the remaining 8-12% of cases are caused by gross deletions of the APC gene.9,10,1
Genetic analysis of the APC gene can provide confirmation of a clinical diagnosis of FAP. Once a mutation is identified in a patient, testing of other family members can help identify carriers, including children, before clinical manifestations are present. Early identification of at-risk family members improves diagnostic certainty and reduces the need for costly screening procedures in those family members who have not inherited the disease-causing mutation.
The Ambry Test: APC AMPLIFIED includes concurrent APC gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 4-18 of the APC gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns and analysis for gross deletions/duplications of the APC gene is performed by the Multiplex Ligation-Dependent Probe Amplification (MLPA) kit, developed by MRC Holland. Specific mutation analysis for individual APC mutations known to be in the family is also available.
Mutations in the APC gene are detectable in up to 88% of individuals affected with classic FAP.12 Detection rates are highest in classic FAP and in individuals with a family history of polyposis.9 The Ambry Test: APC AMPLIFIED is capable of detecting >99% of described mutations in APC.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Minimum DNA Amount of 5μg of DNA at a concentration of ~100ng/μl in 50μl TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 20μg. Store frozen and ship on ice or dry ice.
*Testing Under 18 years of Age: Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique |
|---|---|
| 3040 | APC Gene Sequence Analysis and Deletion / Duplication |
| 3044 | APC Gene Sequence Analysis |
| 3046 | APC Deletion / Duplication Analysis |
| 4660 | MUTYH Gene Sequence Analysis |
| 8720 |
MUTYH Associated Polyposis |
| 8722 |
FAP PLUS Reflex Option |
| 8726 |
FAP PLUS Concurrent |
| Technique | Days |
|---|---|
| APC Gene Sequence Analysis and Deletion / Duplication | 10-21 |
| APC Gene Sequence Analysis | 10-21 |
| APC Deletion / Duplication Analysis | 7-14 |
| MUTYH Gene Sequence Analysis | 14-21 |
|
MUTYH Associated Polyposis |
7-21 |
|
FAP PLUS Reflex Option |
10-28 |
|
FAP PLUS Concurrent |
10-21 |
1. Lipton L et al. The genetics of FAP and FAP-like syndromes. Fam Cancer. 2006; 5(3):221-226. [PMID: 16998667]
2. Petersen GM et al. Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage. Gastroenterology. 1991; 100(6):1658-1664. [PMID: 1673441]
3. Pedace L et al. Identification of a novel duplication in the APC gene using multiple ligation probe amplification in a patient with familial adenomatous polyposis. Cancer Genet Cytogenet. 2008; 182(2):130-135. [PMID: 18406876]
4. Gardner EJ & Richards RC. Multiple cutaneous and subcutaneous lesions occurring simultaneously with hereditary polyposis and osteomatosis. Am J Hum Genet. 1953; 5(2): 139-147. [PMID:13065261]
5. Hamilton SR et al. The molecular basis of Turcot's syndrome. N Engl J Med. 1995; 332(13):839-847. [PMID:7661930]
6. Knudsen AL et al. Attenuated familial adenomatous polyposis (AFAP). A review of the literature. Fam Cancer. 2003;2(1):43-55. [PMID:14574166]
7. Bisgaard ML et al. Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Hum Mutat. 1994; 3(2):121-125. [PMID:8199592]
8. Fodde R et al. APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer. 2001;1(1):55-67. [PMID:11900252]
9. Giardiello FM et al. AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology. 2001;121(1):198-213. [PMID:11438509]
10. Bunyan DJ et al. Dosage analysis of cancer predisposition genes by multiplex ligation-dependent probe amplification. Br J Cancer. 2004; 91(6):1155-1159. [PMID:15475941]
11. Sieber OM et al. Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas. Proc Nati Acad Sci USA. 2002; 99(5):2954-2958. [PMID:11867715]
12. Castellsague E et al. Detection of APC gene deletions using quantitative multiplex PCR of short fluorescent fragments. Clin Chem. 2008; 54(7):1132-1140. [PMID:18487285]