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Biosci Rep. 1986 Aug;6(8):691-708.

A unified theory for the development of cancer.


It is postulated that cancer is the result of genetic and epigenetic changes that occur mainly in stem (precursor) cells of various cell types. I propose that there are three classes of genes which are involved in the development of cancer. These are: Class I, II and III oncogenes. The classification is based on the way the oncogene acts at the cellular level to further the development of cancer. Genetic changes, that is point mutations, deletions, inversions, amplifications and chromosome translocations, gains or losses in the genes themselves or epigenetic changes in the genes (e.g. DNA hypomethylation) or in the gene products (RNA or protein) are responsible for the development of cancer. Changes of oncogene activity have a genetic or epigenetic origin or both and result in quantitative or qualitative differences in the oncogene products. These are involved in changing normal cells into the cells demonstrating a cancer phenotype (usually a form of dedifferentiated cell) in a multistep process. There are several pathways to cancer and the intermediate steps are not necessarily defined in an orderly fashion. Activation of a particular Class I or II oncogene and inactivation of a Class III oncogene could occur at any step during the development of cancer. Most benign or malignant tumors consist of a heterogeneous mixture of dedifferentiated cells arising from a single cell.

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