Despite the plethora of “oncogenes” and “tumor suppressor genes,” the hypothesis that cancer is usually the result of genomic mutations may be wrong. We should at least examine the alternative hypothesis, for which there is considerable evidence, that mutations do not commonly beget cancer, but rather that cancer phenotypes result from confused or aberrant patterns of normal-gene expression; the abnormal patterns are postulated to result from epigenetic mechanisms rather than from mutations. The epigenetic hypothesis that I am proposing suggests that cancers may exhibit mutations primarily because replicative errors at inactive sites in the cancer genome may be repaired slowly or not at all, but the mutations so produced, occurring at already inactivated sites in the genome, may have limited biological significance. Thus, it may be more correct to say that cancers beget mutations than it is to say that mutations beget cancers.

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