The aim is to investigate the possible role of human endogenous retroviruses in the pathogenesis of colon cancer and possibly in its genetic predisposition. In addition, we plan to investigate the possibility that retroviral gene products may provide early markers for the detection of the disease at its initial stages (dysplasia and polyps). Southern blot hybridization will provide information on the pattern of integration of endogenous retroviral sequences in normal colon mucosa and colon tumors. Northern blot analyses will be used to examine the transcription of these sequences, whose pattern of expression can be correlated with particular aspects or stages of the neoplastic disease (possibly including the progression from polyps or dysplasia to adenocarcinoma). Using cDNA cloning and hybridoma technology, we plan to characterize the molecular structure and functional properties of these putative gene products and to use """"""""in situ"""""""" hybridization to validate our biochemical findings. Retroviral gene products may provide specific markers to monitor the initial stages as well as the progression of the neoplastic disease. We will also test the concept of genetic predisposition to colonic cancer by extending our molecular and biochmical approach to the study of hereditary polyposis of colon. Specific proviral units, which behave as vertically transmitted mendelian genes, may constitute the substrate for genetic predisposition to cancer and their expression may correlate with certain clinical or pathologic aspects of colonic neoplasia.
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