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Chapter 079. Cancer Genetics (Part 2)

General Classes of Cancer Genes There are two major classes of cancer genes. The first class comprises genes that directly affect cell growth either positively (oncogenes) or negatively (tumor-suppressor genes). These genes exert their effects on tumor growth through their ability to control cell division (cell birth) or cell death (apoptosis). Oncogenes are tightly regulated in normal cells. In cancer cells, oncogenes acquire mutations that relieve this control and lead to increased activity of the gene product. This mutational event typically occurs in a single allele of the oncogene and acts in a dominant fashion. In contrast, the normal. | Chapter 079. Cancer Genetics Part 2 General Classes of Cancer Genes There are two major classes of cancer genes. The first class comprises genes that directly affect cell growth either positively oncogenes or negatively tumor-suppressor genes . These genes exert their effects on tumor growth through their ability to control cell division cell birth or cell death apoptosis . Oncogenes are tightly regulated in normal cells. In cancer cells oncogenes acquire mutations that relieve this control and lead to increased activity of the gene product. This mutational event typically occurs in a single allele of the oncogene and acts in a dominant fashion. In contrast the normal function of tumorsuppressor genes is to restrain cell growth and this function is lost in cancer. Because of the diploid nature of mammalian cells both alleles must be inactivated to completely lose the function of a tumor-suppressor gene leading to a recessive mechanism at the cellular level. From these ideas and studies on the inherited form of retinoblastoma Knudson and others formulated the two-hit hypothesis which in its modern version states that both copies of a tumor-suppressor gene must be inactivated in cancer. The second class of cancer genes the caretakers does not directly affect cell growth but rather affects the ability of the cell to maintain the integrity of its genome. Cells with deficiency in these genes have an increased rate of mutations in all the genes including oncogenes and tumor-suppressor genes. This mutator phenotype was first hypothesized by Loeb to explain how the multiple mutational events required for tumorigenesis can occur in the lifetime of an individual. A mutation phenotype has now been observed in cancer at both the nucleotide sequence and chromosomal levels. Mechanisms of Tumor-Suppressor Inactivation The two major types of somatic lesions observed in tumor-suppressor genes during tumor development are point mutations and large deletions. Point mutations in the .