Last update: 05/06/2006
Background to disease
OMIM 175100
Familial adenomatous polyposis (FAP), characterised by numerous adenomatous polyps, is an inherited predisposition to colorectal cancer. Without intervention, the pre-malignant condition progresses to carcinoma. It is transmitted as an autosomal dominant trait, with some variability in the clinical presentation, including presence of extracolonic lesions, and severity, but with full penetrance.
Germline mutations of the APC gene underlie FAP. APC functions as a tumour suppressor gene, with a second, somatic, mutation event believed to be critical for tumour development. The vast majority of mutations disrupt the coding region, predicting premature termination of the protein. Globally, the very large terminal exon, exon 15, is the mutation hotspot. However, the most common mutation in Yorkshire is R283X in exon 8. Complete or partial deletions of APC have also been found in FAP. The product of the APC gene interacts with a number of proteins, amongst them beta-catenin, and appears to participate in the regulation of many cellular functions like adhesion, signaling, and cytoskeletal plasticity.
Laboratory Analysis
Contact scientist: Lampros Mavrogiannis
|
|
Test |
Target reporting time (working days) |
|
1. |
R283X |
20 |
|
2. |
MLPA dosage analysis |
20 |
|
3. |
Sequencing of specific exons (known mutations) |
20 |
|
4. |
Full coding region sequencing |
40 |