Clonality of malignant-tumors (review).

Heterogeneous descendants are continuously produced in tumor cell evolution, although the first step of carcinogenesis may involve a single clone. From the data obtained by molecular biology, we have to recognize that the 'clonality of tumor' proliferated from a single clone does not confirm the genetic identity of tumor cell society. The so-called 'multi-hit hypothesis' can not explain this heterogeneity, since this hypothesis only describes serial changes of genes in carcinogenesis. However, genetic alterations actually accumulate progressively after carcinogenesis until the end of total cell death. Genetic alterations in tumor evolution are a stochastic process rather than a non-stochastic one, since 'neutral evolution' in molecules occurs in micro-environments, It is an essential concept that retrospective analysis can never demonstrate the clonal origin of tumors, because the genetic pool of tumor cell society is unstable and changes proliferation-dependently.