Aneuploidy in yeast: a contributor or remnant of tumorigenesis

Abstract

It is widely accepted that cancer results from the accumulation of mutations in the genes that directly control cell birth or cell death. But the mechanisms through which these mutations are generated are the subject of longstanding debate primarily between two models; one holds that cancer specific phenotypes are the result of multiple, specific gene mutations where mutation either generate dominant oncogenes or inactivates recessive tumor suppressor genes, and the other holds that cancer specific phenotypes are the result of the thousands of normal genes whose dosage is altered by aneuploidy. The proponents of mutation hypothesis postulate that among 6 to 10 mutations are necessary for carcinogenesis. Assuming mutation rate is 10-6/cell/generation, and 6 mutations are involved in cancer formation, we can calculate that only 1 in 10³⁶ human cells would ever become cancer cells. Since human consist of 10¹² cells, only 1 in 10²⁴ humans would get cancer. In other words, cancer would hardly exist. The mutation hypothesis also predicts that carcinogens can mutate cellular genes. On the other hand, about 50% of carcinogens are categorized as non-mutagens. Thus, the mutagenic reactions of genotoxic carcinogens may be coincidental rather than causal factors for tumorigenesis. In this workshop, we presented the experimental results which support the hypothesis that aneuploidy is the cause rather than a consequence of tumorigenesis.