Differential Gene Expression in Primary Colonic Tissue from Control, FAP and AFAP Patients Reveals Unique Signatures with Diagnostic Potential

Background Familial adenomatous polyposis (FAP) is a colon cancer syndrome with a prevalence of 1:10,000. Patients have 100's to 1000's of precancerous colonic polyps and nearly 100% risk of developing colon cancer at an average age of 39 years in the absence of colon surveillance and surgery. Mutations in the APC gene lead to FAP as well as an attenuated form (AFAP) which presents with variable phenotypic expression, reduced polyp numbers and reduced cancer risk as compared to FAP. Current methods for the clinical diagnosis of genetic diseases most commonly involve analysis of germline DNA. Germline DNA-based diagnosis can be incomplete, for example no mutation is found in approximately 20% of FAP and 50% of AFAP patients. The objective of this study is to determine a molecular profile of the colonic epithelia from patients with APC mutations leading to FAP or AFAP then to use this information to establish a gene expression signature for diagnosis and for better understanding of the disease in the primary affected tissue.