Acquired Mutation

Also known as somatic mutation, acquired mutation is an alteration of genetic matter that occurs after the time of conception and affects somatic cells (as opposed to mutations that affect germ cells). A principal consequence of affecting only somatic cells is that such mutations cannot be passed to offspring. However, acquired mutations are normally transmitted to all cells descended from the original mutant cell, giving rise of a clone (colony) of cells bearing the acquired mutation. Mutations of this sort are critical in the development of various cancers.

The Weinberg Progression Model identifies six acquired characteristics shared by all tumors, but the relative role inheritance and acquired 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. Pro-to-oncogenes are normal genes that encode proteins responsible for normal cellular growth. When subject to acquired mutation, proto-oncogenes may become oncogenes, leading to unregulated cell growth and proliferation. 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. Individuals who are born heterozygous for a tumor suppressor gene (via inherited mutation) require only one acquired mutation event to alter the antigrowth signaling pathway, whereas individuals born without such a hereditary mutation require two acquired mutation events to yield the same outcome.

For example, mutation to the HER2 gene contributes to the uncontrolled growth of approximately 30 percent of breast cancers. Targeting this over expression mutant is a key strategy in chemotherapy for breast cancer. The retinoblastoma tumor suppressor protein, pRb, needs to be present in at least one copy in order to prevent the development of retinoblastoma. In individuals who inherit only one wild-type allele, an acquired mutation can precipitate sporadic retinoblastoma.