Somatic Mutation

Cancer-Related Genes Subject to Somatic Mutation

The Weinberg Progression Model identifies six somatic characteristics shared by all tumors, but the relative role inheritance and somatic mutation play in each characteristic is a complex function of the disease in question, the family history of the subject, and other factors such as environmental exposure.

Of greatest importance in the study of modern medical practices are self-sufficiency in growth factors and the loss of inhibition to growth factors. Proto-oncogenes are normal genes that encode proteins responsible for normal cellular growth. When subject to somatic mutation, proto-oncogenes may become oncogenes, leading to unregulated cell growth and proliferation through self-sufficiency in growth signals.

Typically, oncogenes act in a dominant manner, needing only one mutated copy (out of two) to have a physiological impact. In contrast, tumor suppressor genes, which encode proteins responsible for antigrowth signals, typically function in a recessive manner and require mutations to both copies before physiological consequences manifest themselves in insensitivity to antigrowth signals. Individuals who are born heterozygous for a tumor suppressor gene (via inherited mutation) require only one somatic mutation event to alter the antigrowth signaling pathway, whereas individuals born without such a hereditary mutation require two somatic mutation events to yield the same outcome, a phenomenon known as the loss of heterozygosity.

Somatic Mutation in Atypical Inheritance

In the absence of molecular genetic techniques, many disease states with simple Mendelian inheritance can still be accurately studied. A clinical diagnosis of such a disease can often allow a physician or genetic counselor to provide information on the expected likelihood that such a disease state will be passed on to offspring or that offspring will be carriers for the disease state. Somatic mutation may, however, lead to incorrect conclusions in the absence of confirmation via molecular genetic techniques.

Suppose a father suffers from an autosomal dominant disorder. He expects half of his offspring to be affected and may, for this reason, choose not to reproduce. However, good genetic counseling may reveal that neither of the man's parents were afflicted with the disease. This leads to the conclusion that the autosomal dominant allele was not inherited, it was acquired via a somatic mutation. Genetic testing can confirm this determination and [Page 1584]allow counselors to reassess the risk of transmission for the potential father.