Figure 1

The speciation theory of cancer. This theory postulates that carcinogens or spontaneous events induce aneuploidy, namely losses or gains of entire chromosomes or parts of chromosomes at rates, termed m1. By unbalancing thousands of genes aneuploidy automatically destabilizes the karyotype, and thus catalyzes random karyotypic variations at aneuploidy-dependent rates, termed m2. Selections of variants with proliferative phenotypes form non-clonal hyperplasias* with persistently varying karyotypes. Variants without proliferative phenotypes perish. Very rare karyotypic variations form new cancer species with individual clonal karyotypes at very low rates, termed m3. Despite destabilization by their congenital aneuploidies, cancer karyotypes are stabilized within narrow margins of variation by clonal selections for cancer-specific autonomy of growth. Within these margins cancer karyotypes are clonally flexible at aneuploidy-dependent rates, termed [m2]. To generate new cancers all clonal aneusomies of cancers must be joined in single-steps, rather than gradually, because of the inherent instability of non-cancerous or pre-cancerous aneuploidy. Since this mechanism is very inefficient, it predicts long latent periods from carcinogens to cancers and individual clonal cancer karyotypes. *Hyperplasias are defined here according to the Oxford American Dictionary as “The enlargement of an organ or tissue caused by an increase in the reproductive rate of its cells, often as an initial stage in the development of cancer.”