APC -Associated Polyposis conditions including Familial Adenomatous Polyposis (FAP), attenuated FAP, Gardner syndrome, and Turcot syndrome are a group of autosomal dominant conditions caused by mutations in the APC gene. FAP is a colon cancer predisposition syndrome where hundreds to thousands of adenomatous polyps develop in the colon in the second to third decade of life and may include gastroduodenal polyps (both adenomatous and fundic gland polyps). Classical FAP has 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.
The APC gene 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. More than 300 different germline APC mutations have been identified, almost all of which are found in the coding region and result in the truncation of its encoded APC protein. Most of these mutations are nonsense mutations, nucleotide alterations at splicing sites, or small insertions or deletions, which account for ~80% of the all the APC gene mutations. In addition, large gene rearrangements have been identified and estimated to account for up to ~20% of the mutations in the APC gene (1-4). Well-characterized gross alterations of APC have been reported in both the typical FAP phenotype, and a phenotype consistent with that of AFAP. Sequencing and deletion/duplication screening for mutations in the APC gene is available at the Baylor Medical Genetics Laboratories.
Reasons For Referral:
- Confirmation of clinical diagnosis of APC -associated polyposis conditions
- Presymptomatic testing in families in which a familial mutation has been identified
- Prenatal testing for known familial mutations.
Testing Methodology:
Bi-directional sequence analysis is performed on all 15 coding exons and splice sites of the APC gene. Gross deletions and duplications of the APC gene are screened by Multiplex Ligation-dependent Probe Amplification (MLPA). Gene regions showing dosage variations are subsequently confirmed by using alternative methods, which can include real-time PCR, long range PCR and intragenic SNP marker analysis when applicable.
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:
APC Comprehensive (Sequencing & Deletion/Duplication Analysis) - Index: 4 weeks
APC ONLY Sequencing - Index: 4 weeks
Known Familial Mutation - Sequencing: 3 weeks
Deletion/Duplication by MLPA: 3 weeks
APC Comprehensive (Sequencing & Deletion/Duplication Analysis) - Index: 83904x29, 83912x2, 83909x59, 83898x29, 83894, 83891, 83900, 83901x21, 83914x21
APC ONLY Sequencing - Index: 83904x28, 83912, 83909x52, 83898x28, 83894, 83891
Known Familial Mutation - Sequencing: 83904x2, 83912, 83909x2, 83898, 83891, 83894
Deletion/Duplication by MLPA: 83891, 83900, 83901x21, 83909, 83912, 83914x21
Forms:
>> Cancer
DNA Requisition
>> Prenatal
Requisition
References:
- Su LK. (2000) Hum. Genet. 106: 101-107
- Wu G, et al. (2001) Genet. Test. 5: 281-290.
- Bertario L, et al. (2003) J. Clin. Oncol. 21: 1698-1707
- Mueller, et al. (2004) Genet. Test. 8: 248-256.
Test Codes:
APC Comprehensive (Sequencing & Del/Dup Analysis): 6720
APC ONLY - Sequencing: 6087
Known Familial Mutation by Sequencing: 6089
Deletion/Duplication by MLPA: 6721
Prenatal (Known Familial Mutation Only): 6090
Prenatal Deletion/Duplication (Known Familial Mutation Only): 6722
|