Chaotic genomes make chaotic cells: the mutator phenotype theory of carcinogenesis applied to clinicopathological relationships of solid tumors.

Abnormalities of cell morphology and chromosomes have been identified as features of the pathology of tumors for more than 100 years. However, no theory of carcinogenesis until recently has provided a basis for relating them either to each other or to the clinical behavior of individual tumors in many patients. The mutator phenotype theory is based on large numbers of mutations occurring chaotically (randomly, unpredictably, and variably from cell to cell) in individual tumors. Chaotic mutation clearly parallels both the often-observed chaotic morphology of tumors and the frequently unpredictable relationship of these morphologies to clinical behavior. Possible implications of this concept for staging, grading, multifocality, and therapy of cancers are discussed.