This is my explanation. In some cases it is result of thymidylate stress. This is a cdc21 (TYMS) mutant cell line of S. cerevisiae with thymidylate added to a center well establishing a radial gradient of deoxynucleotide. There is only a narrow annulus of normal OXPHOS cells visualized by tetrazolium staining. Cells near the center are heavily mutagenized but remain 2n. Cells near the periphery have numerous chromosome breaks and rearrangements. I am suggesting that this experiment mimics a breast stem cell tumor that originated with permanent TYMS dysregulation.
Genetic instability which includes both numerical and structural chromosomal abnormalities, is a hallmark of cancer.Two prominent features of cancer cells are abnormal numbers of chromosomes (aneuploidy) and large-scale structural rearrangements of chromosomes.These genetic changes perpetuate the malignant state and are preceded by metabolic derangements. Disregulation, chaos, entropy are common in cells lacking the necessary energy to provide the needed order, organization and communication to achieve metabolic balance.
Maybe it is related to hypoxia-induced reactive oxygen species in the periphery of tumors.
Dear colleague.
Thymidylate synthetase in many processes can not talk about mimic a breast stem cell tumor, as it is a co-factor in many (not only cancer) processes, and prognostic biomarker in non-small-cell lung cancer and colorectal cancer wild-type and many other processes.
Regards
It is my view that TYMS is a prognostic indicator in many cancer types because it is causally related to disease etiology in the first place. An important target of chemotherapy for many decades for the same reason. Under or over expression of TYMS (or both in the same tumor population) is central to the malignant enterprise.
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