FAMILIAL ADENOMATOUS POLYPOSIS (FAP): APC Sequencing
DNA ANALYSIS
Also see: Familial Adenomatous Polyposis - Deletion/Duplication Assay

Familial adenomatous polyposis (FAP) is an autosomal dominant condition, which predisposes the mutation carrier to colorectal cancer in early adulthood. The condition is characterized by hundreds to thousands of adenomatous polyps in the colon that usually develop in the second to third decade of life, and may include gastroduodenal polyps (both adenomatous and fundic gland polyps). Classical FAP had been considered to have no associated extraintestinal manifestations; however, a variant condition, Gardner syndrome, does manifest additional features including osteoma of the mandible and calvarium, dental abnormalities (supernumerary teeth), and epidermoid cysts. Desmoid tumors occur in about 10% of patients and may be associated with significant morbidity and mortality. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is commonly associated with Gardner Syndrome and has been suggested as a useful marker to detect patients at risk in FAP families. A milder condition, termed Attenuated FAP (AFAP), lacks the classical features of FAP, with patients having fewer polyps and an older age of onset. As many as 1 in 5000 individuals in the U.S. population may be affected with FAP. Cytogenetic and linkage studies have localized the gene responsible for FAP and AFAP to chromosome 5q21 and its genomic organization has been characterized. FAP has been linked to germline mutations of the APC gene that encodes a protein with 2,843 amino acids that has important functions in the regulation of cell growth. Similar to other tumor suppressor genes, both APC alleles are inactivated by mutation in colon tumors, resulting in the loss of full-length protein in tumor cells. These findings have facilitated the identification of specific mutations responsible for FAP in approximately 80% of patients and their at risk relatives. Molecular genetic testing for FAP is available at the Baylor Diagnostic Sequencing Laboratory.

Reasons for Referral:

Confirmation of clinical diagnosis of FAP and AFAP
Presymptomatic testing in FAP/AFAP families in which a familial mutation has been identified.

Testing Methodology:

Full Sequencing: A PCR-based assay is used to amplify all 15 exons of the APC gene. Direct sequence analysis of PCR products corresponding to the entire APC coding region is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult/Child: Minimum 6-14 cc.
Requisition form must accompany the specimen. Prior to any genetic testing, we recommend genetic counseling and we request that the subject sign our consent statement and submit it with the sample. To receive forms, additional information or specimen collection kits, please contact the laboratory. Prenatal available for known familial mutation only. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 3 weeks

CPT Codes and Prices:

Index: 83904x28, 83912, 83909x52, 83898x28, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Wu G, et al. (2001) Genet. Test. 5: 281-290.
2. Bertario L, et al. (2003) J. Clin. Oncol. 21: 1698-1707.

Shipping Information

Forms:

>> Cancer DNA Requisition
>> Prenatal Requisition

Test Codes:

Index: 6087
Known Familial Mutation: 6089
Prenatal (Known Familial Mutation Only): 6090