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Gene Expression Profiling in Familial Adenomatous Polyposis Adenomas and Desmoid Disease

DOI: 10.1186/1897-4287-5-2-79

Keywords: gene expression profiling, FAP, adenomos, desmoid tumours

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Familial adenomatous polyposis (FAP) is a rare form of colorectal cancer caused by germline mutations in the adenomatous polyposis coli (APC) gene. Approximately 70–90% of FAP patients have identifiable germline mutations in APC [1,2]. FAP is clinically characterized by the formation of hundreds to thousands of adenomas that carpet the entire colon and rectum [3]. Although initially benign the risk of malignant transformation increases with age such that, if left untreated, colorectal carcinoma usually develops before the age of 40 years [4].Loss of APC results in dysregulation of the Wnt signalling pathway that leads to the constitutional activation of the transcription factor Tcf-4, which has been associated with adenoma formation [5]. Alterations in Wnt signalling cause stem cells to retain their ability to divide in the upper intestinal crypt, thereby forming monocryptal adenomas [6]. Eventually the adenomas may acquire metastatic potential, resulting in carcinoma development [7]. Not all adenomas will progress to malignant tumours; however, due to the abundance of adenomas carcinoma development is virtually assured [8].Apart from the apparent loss of APC function, little is known about the molecular processes involved in adenoma initiation [6]. Similarly, the molecular events occurring during the transformation of adenomas into carcinomas are poorly understood, as are the mechanisms that underlie the development of extra-colonic disease in FAP.It is well established that FAP patients are susceptible to benign extra-colonic tumours, including desmoid tumours [3]. Although rare in the general population, desmoids occur in approximately 10% of FAP patients and they are the second most common cause of death [9]. Desmoid tumours are poorly encapsulated and consist of spindle-shaped fibroblast cells with varying quantities of collagen [10]. Despite their apparent inability to metastasize, desmoid tumours can be extremely aggressive [11].It has been speculated that de


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