Genetics of Tumor Suppressor Genes

Mutations in tumor suppressor genes can arise spontaneously by exposure to a mutagenic substance such as ultraviolet light or certain chemi division that produces new cells cals. In such cases, only the mutated cell and its descendants will be affected. Mutations can also be inherited from a parent or arise early in development. In these cases, almost all the cells of the body will inherit the same mutation.

A mutation in a single tumor suppressor gene is usually not enough to cause cancer. This is because each cell contains two copies of each gene, one inherited from each parent. Most cancer-causing mutations cause a loss of function in the mutated gene. Often, having even one functional copy is enough to prevent disease, and two mutations are needed for cancer to develop. This is known as the "two-hit" model of carcinogenesis.

This model was first described in retinoblastoma, a common cancer of the retina. The affected gene (called the retinoblastoma gene) is a tumor suppressor. Spontaneous (noninherited) mutations are rare, but since there are many millions of cells in the retina, several of them will develop the gene mutation over the course of a lifetime. It would be very unlikely, though, for a single cell to develop two spontaneous mutations (at least in the absence of prolonged exposure to carcinogens), and thus noninherited retinoblastoma is very rare. When it occurs, it almost always affects only one eye—the eye in which the unlucky doubly hit cell resides.

If, however, a person inherits one copy of an already mutated gene from one parent, every cell in the eye starts life with one "hit." The chances are very high that several cells will suffer another hit sometime during their life. The chances are thus very high that the person will develop retinoblastoma, almost always in both eyes, since the necessary second hit is common enough that cells in both eyes will be affected. Because inheriting a single copy of the mutated gene is so likely to lead to the disease, the gene is said to show a dominant inheritance pattern.

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