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. 1983 Oct;48(4):463–475. doi: 10.1038/bjc.1983.219

5-Methylcytosine depletion during tumour development: an extension of the miscoding concept.

J Nyce, S Weinhouse, P N Magee
PMCID: PMC2011508  PMID: 6354237

Abstract

We propose a general model for neoplastic development which postulates that the loss of methyl groups from 5-methylcytosines (5-mC) involved in the control of gene expression may initiate neoplastic transformation and give rise to the aberrant phenotype of the transformed cell. Interference with normal patterns of methylation can be envisioned to occur by a number of mechanisms: as a result of carcinogen-induced G:C leads to A:T transition leading to a loss of potentially methylatable cytosines; by mutations or chromosome rearrangement which disrupt the integrity of active DNA methylase genes; by separating methylated repressor regions of the genome from the genes they control; by direct interference with DNA methylation, as proposed for ethionine and 5-azacytidine; by spontaneous deamination of 5-mC to thymine, leading to accumulation of 5-mC:G leads to T:A transitions, by virus-induced perturbations in host cell methylation patterns; and by activation of DNA demethylases.

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Selected References

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