The Epigenetic Theory of Carcinogenesis: p53 as the Guardian of The Epigenome
Journal Title: Journal of Oncology and Cancer Research - Year 2017, Vol 1, Issue 1
Abstract
The principal advantage of the hypothesis that the multiple phenotypic abnormalities characteristic of malignant and pre-malignant cells result from epigenetic disorder is that it accounts for the wide spectrum of anomalies exhibited by these cells without recourse to postulating a raised mutation rate. The basic proposal is that derangement of the process of copying the epigenetic pattern during proliferation of differentiated stem cells enables dysregulated genetic re-programming and de-differentiation of the affected progeny, a phenomenon that might be termed “epimutation”. This results in the generation of abnormal clones expressing divergent structural and functional characteristics, some of which embue the cells with malignant properties. The epigenetic theory of carcinogenesis postulates that the initiating mutations cause deranged vertical transmission of the epigenetic pattern established in proliferating differentiated stem cells. The failure of fidelity of copying the epigenetic pattern results in changes of expression of genes, including the re-expression of previously silenced genes characteristic of earlier developmental stages or of other tissues. The mechanism involves the generation of chromosomal abnormalities and deranged cellular organization. Some clones acquire properties that render them capable of transgressing tissue boundaries and proliferating in distant sites, i.e. they exhibit malignant behavior. The mathematical features of the theory are concomitant with established accounts of age-specific incidence of adult human malignancies and the proposed mechanism accounts for the known characteristics of cancer.
Authors and Affiliations
Patrick A Riley
Keywords
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- EP ID EP249309
- DOI 10.28967/jocr.2017.01.17002
- Views 110
- Downloads 0
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