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See also: tumor suppressor gene, antioncogene.
Genes of mutations that can permit or induce uncontrolled cellular proliferation and malignant change are of two types: protooncogenes and tumor suppressor genes (antioncogenes). Protooncogenes encode proteins that stimulate DNA synthesis and cell division, including peptide growth factors and their cellular membrane receptors; second-messenger cascade proteins, which transmit information from cell membrane to nucleus; and nuclear transcription factors, which control gene expression by binding to DNA. Conversion of a protooncogene to an oncogene by amplification, translocation, or point mutation can lead to unrestrained cellular proliferation and malignant change. Only 1 copy (allele) of a protooncogene need undergo mutation to induce tumor formation. Protooncogenes are not involved in inherited cancer syndromes, with the exception of the RET protooncogene in multiple endocrine neoplasia. Tumor suppressor genes (antioncogenes), which encode proteins that normally serve to restrain cell proliferation, can be inactivated by point mutation, deletion, or loss of expression. An inherited mutation in 1 copy of a tumor suppressor gene is the basis of most familial predispositions to cancer. Malignant cellular proliferation does not occur until the remaining, functional copy of the gene is inactivated by mutation or by deletion of part or all of its chromosome. In a person born with two normal copies of a tumor suppressor gene, both must be inactivated by mutation before tumor formation occurs. BRCA1 and BRCA2, which predispose to familial early-onset breast cancer and ovarian cancer, are tumor suppressor genes.