People who inherit one copy of the Rb (retinoblastoma) gene that is normal and one copy that is mutated—that is, people who are heterozygous for Rb—have a greatly increased risk of cancer

Question

Given this information, do you agree or disagree with the following statement? Explain your answer.

The Rb mutation must have a dominant effect, which means that it must result in an increase in Rb function. Thus, Rb in its mutant form must be an oncogene.

Answer 1

Disagree. It is true that the Rb mutation is dominant, in the sense that a person who is heterozygous (inherits one normal copy and one mutant copy of the gene) is likely to show the mutant trait (that is, will be cancer-prone). However, this does not mean that the mutation in Rb causes an increase in Rb gene function; in fact, the opposite is true—the propensity for cancer arises from a loss of Rb gene function. Therefore, Rb should be classified as a tumor suppressor gene and not as an oncogene. Most people have two functional Rb genes in each of their cells. Thus, for one of their cells to turn cancerous by losing Rb function, both copies of the gene in that cell must be inactivated or lost, a two-step process. However, in a person born lacking one copy of the Rb gene, each cell is only one step away from a complete loss of Rb function. Consequently, such a person has a high risk that at least one of the cells in the body will undergo a mutation that precipitates cancer. In this way, at the level of the whole person, the Rb loss-of-function mutation is dominant, even though at the level of the individual cell it is recessive.