Genetic mosaicism and the control of cancer.
The susceptibility of animal cells to certain lethal agents, including a variety of cytotoxic drugs, is genetically determined; cells which are otherwise identical may therefore differ in terms of which agents are lethal for them. If such genetic diversity existed within a tissue, exposure to any of these lethal agents would not destroy every cell, but only that fraction of the population that was susceptible. In contrast, if a clone of malignant cells arose from any single cell within such a tissue, the entire malignant clone should be susceptible to destruction by whatever agent its progenitor cells was susceptible to. Treatment of a tumor in a host whose tissues displayed such genetic mosaicism might therefore possess the potential for destroying all tumor cells, at the cost of destroying only a fraction of the normal cells. Prophylactic induction of such mosaicism in normal hosts by genetic manipulation represents a potential future strategy for cancer control. Evidence is presented suggesting that women heterozygous for deficiency of the enzyme hypoxanthine-guanine phosphoribosyl-transferase may constitute naturally occurring examples of such exploitable mosaicism.
D005818:Genetic Engineering; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase; D008954:Models, Biological; D009030:Mosaicism; D009369:Neoplasms / Q000517:prevention & control*
D007041:Hypoxanthine Phosphoribosyltransferase