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Genetic and epigenetic changes in early carcinogenesis

Studies of human epithelial cells and fibroblasts from healthy individuals are providing novel insights into how early epigenetic and genetic events affect genomic integrity and fuel carcinogenesis. Key epigenetic changes, such as the hypermethylation of the p16 promoter sequences, create a previously unappreciated pre-clonal phase of tumorigenesis in which a subpopulation of epithelial cells is positioned for progression to malignancy [1]. These key changes precede the clonal outgrowth of premalignant lesions and occur frequently in healthy, disease-free individuals [2]. Prior work from our laboratory has shown that surrounding stroma can dramatically influence tumorigenesis. Proper stromal-epithelial interactions can actually suppress the expression of preneoplastic phenotypes in epithelial cells and, conversely, altered stromal-epithelial interactions can promote the probability that preneoplastic lesions progress to malignancy [3]. Understanding more about these early events should provide novel molecular candidates for prevention and therapy of cancer.


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  2. Cancer Cell. 2004, 5: 263-10.1016/S1535-6108(04)00023-6.

  3. Cancer Res. 1999, 59: 5002-

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Tlsty, T. Genetic and epigenetic changes in early carcinogenesis. Breast Cancer Res 7 (Suppl 2), S.14 (2005).

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