Somatic mutation/neodifferentiation/selection and the origins of human cancers.
For some time, there has been a confusing and often frustrating difference of opinion amongst molecular pathologists and biologists regarding the relative involvement of somatic mutation vs. altered differentiation (neodifferentiation) in human carcinogenesis. This distinction, however, has led to opposing biological viewpoints which have a found alignment with opposing political viewpoints. While this distinction may have historical rationale, it has little biological basis, and it is possible to construct an integrative viewpoint which reconciles the "very different points of view and styles of argument" resulting from its use. The general evidence available suggests that most human epithelial cancers are caused by chemicals and radiations capable of inducing local mutations in regulatory sequences of genomic DNA, leading, perhaps through genetic transposition, to a mis-programming of natural genomic information expression. In this viewpoint, somatic mutation and altered differentiation are not mutually exclusive mechanisms as often implied, but, in all likelihood, are temporally related mechanisms; and human cancer thus becomes fundamentally a disease of cellular differentiation caused by somatic mutations.
D002454:Cell Differentiation; D004848:Epithelium / Q000502:physiology; D006453:Hemoglobinopathies / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology