Characteristic of the test: (includes 1 gene) APC (OMIM # 611731) - exon 16 of the APC gene

Basic characteristics of the clinical phenotype: 
Familial Adenomatous Polyposis (FAP1; OMIM #175100) is a hereditary cancer syndrome clinically characterized by the development of hundreds to thousands of polyps in the colon or rectum. Without treatment, almost all patients with FAP develop colorectal cancer by the age of 40. In addition, patients with FAP are predisposed to develop desmoid tumors, small bowel cancer, thyroid carcinoma, hepatoblastoma, and medulloblastoma.

FAP is an autosomal dominant disease which results from a germline mutation in the Adenomatous Polyposis Coli (APC) gene. More than 1700 germline mutations have been found in APC genes and 85 - 90% are nonsense or frameshift mutations that result in a functionally inactive protein product. The remaining 10–15% are due to large deletions and duplications. The germline mutations are localized in the coding regions of the gene. Acute FAP (developing more than 1000 colorectal polyps) is usually seen in patients carrying mutations in codons 1250 to 1464. In contrast, patients with attenuated FAP (developing fewer than 100 colorectal polyps) usually characterized by mutations at the very beginning (5' end) and at the very end (3' end) of the gene, or in an alternative splice variant of exon 9.

Reason for Referral/Clinical Significance:
Patients with a diagnosis of Familial Adenomatous Polyposis (FAP) or relatives of patients with an APC gene aberration are referred for investigation of the nearby mutational status of the APC gene. This assay was designed to study germline mutations and is not suitable for studying somatic mutations in tumor tissue.

Interpretation of results:

· Mutations found in the APC gene allows the diagnosis of Familial Adenomatous Polyposis (FAP).

· Finding mutations in the APC gene allows identification of a predisposition in an asymptomatic family member with a family history of colorectal carcinoma.

· The genetic counselor will interpret and answer all questions about your result.

Method: Sanger sequencing

The method involves bi-directional DNA sequencing of all 15 coding exons (2-16) and intron-exon boundaries of the APC gene. The laboratory offers single exon or exon pair sequencing in relatives of patients to determine carrier status in cases where the mutation is known (Tests #182 and 183).

Sensitivity of the method: 99.5%

What does the test involve?

· DNA isolation and sample storage.

· Direct sequencing of target genes/gene regions to detect pathogenic mutations.

· Forming a written result of the genetic test.

· Diagnostic interpretation of results and genetic counseling.

Biological material: Venous blood or DNA

For more information, please read the "Biological material requirements and shipping information" carefully.