Aneuploidy vs. gene mutation hypothesis of cancer: Recent study claims mutation but is found to support aneuploidy

For nearly a century, cancer has been blamed on somatic mutation. But it is still unclear whether this mutation is aneuploidy, an abnormal balance of chromosomes, or gene mutation. Despite enormous efforts, the currently popu lar gene mutation hypothesis has failed to identify cancer-specific mutatio ns with transforming function and cannot explain why cancer occurs only man y months to decades after mutation by carcinogens and why solid cancers are aneuploid, although conventional mutation does not depend on karyotype alt eration. A recent high-profile publication now claims to have solved these discrepancies with a set of three synthetic mutant genes that "suffices to convert normal human cells into tumorigenic cells." However, we show here t hat even this study failed to explain why it took more than "60 population doublings" from the introduction of the first of these genes. a derivative of the tumor antigen of simian virus 40 tumor virus, to generate tumor cell s, why the tumor cells were clonal although gene transfer was polyclonal, a nd above all, why the tumor cells were aneuploid. If aneuploidy is assumed to be the somatic mutation that causes cancer, all these results can be exp lained. The aneuploidy hypothesis predicts the long latent periods and the clonality on the basis of the following two-stage mechanism: stage one, a c arcinogen (or mutant gene) generates aneuploidy; stage two, aneuploidy dest abilizes the karyotype and thus initiates an autocatalytic karyotype evolut ion generating preneoplastic and eventually neoplastic karyotypes. Because the odds are very low that an abnormal karyotype will surpass the viability of a normal diploid cell, the evolution of a neoplastic cell species is sl ow and thus clonal, which is comparable to conventional evolution of new sp ecies.