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New approach for improvement of early diagnosis and prediction in familial adenomatous polyposis coli (FAP) by genetic analysis of skin involvement - APC mutations and their influence to lesions of skin
| Third-party funded project |
| Project title |
New approach for improvement of early diagnosis and prediction in familial adenomatous polyposis coli (FAP) by genetic analysis of skin involvement - APC mutations and their influence to lesions of skin |
| Principal Investigator(s) |
Itin, Peter
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| Organisation / Research unit |
Departement Biomedizin / Dermatology (Itin) |
| Project start |
01.12.2009 |
| Probable end |
30.11.2010 |
| Status |
Completed |
| Abstract |
Background: Familial adenomatous polyposis (FAP) is an autosomal-dominant disorder with a complete penetrance characterized by inheritance of colorectal cancer. It is caused by mutations in the adenomatous polyposis coli gene (APC) on chromosome 5 and can be accompanied by different skin lesions. These skin lesions arise in patients with APC mutation, also called Gardner syndrome, more often than in the normal population. Nevertheless, cause of the skin lesions as well as connections between skin lesion and mutation site in the APC are scarcely investigated and poorly understand. Occurrence and expression of skin lesions in FAP patients vary between individuals even in families with the same APC mutation. Currently it is impossible to use skin lesions as a predicting factor, even though some people develop skin lesions like fibromas or lipomas before colorectal adenomas or carcinomas. Missing data are one of the main reason for that.
Working Hypothesis: 1. Types of specific skin lesions, like epidermal cysts, fibroma, and lipomas, are associated with APC. 2. Origin of formation is a second APC mutation, followed by mutations in further cell cycle regulating genes, similar to the process in colon polyps and adenomas. 3. In otherwise healthy individuals sporadic skin lesions of the same type develop analog to those in patients with Gardner syndrome.
Specific aims: 1. To determine differences in the gene expression between specific skin lesions and healthy skin of patients with Gardner syndrome (FAP). 2. To identify the genes, which are responsible for the origin or are involved in the formation of these skin lesions. 3. To characterize analogies to the development of comparable skin lesions in otherwise healthy persons. 4. To investigate possible differences between individuals with Gardner syndrome and healthy individuals.
Experimental design: By systematic skin examination of FAP patients we identified Gardner specific skin lesions in more than 40 patients until now. Research analysis focus on comparative expression analyses using biopsied skin tissue from FAP patients, lesional and healthy, as well as healthy controls after informed consent. Exemplary samples will be performed by microarrays to identify regulated RNAs / cDNAs and first associations between skin lesions and the genomic background regarding the congenital APC mutation. Data thus obtained will be verified on all residual samples by special type of real-time PCR (TaqMan® Gene Expression Assay).
Expected value of the proposed project: In some FAP patients skin lesions may appear before colorectal adenomas manifest. In these cases skin lesions would allow a presymptomatic diagnosis of FAP and an early treatment before a colorectal cancer is developed. Our detailed analysis of formation and regulation of FAP-specific skin lesions, such as epidermal cysts, fibroma, and lipoma, will improve the knowledge about the pathomechanisms of these lesions and could eventually define critical molecular steps in development of extracolonic lesions. Our findings could be the basis to an improved early diagnosis of FAP patients by skin lesions. |
| Financed by |
Foundations and Associations
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14/05/2024
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