Chromosomes and Cancer: Inactivation of Tumor Suppressor Genes
Harris et al.(1969) showed that the fusion of normal and malignant cells produced hybrid cells that were generally nonmalignant. Rarely, however, a hybrid cell gave rise to malignant subclones. These always showed some loss of chromosomes derived from the normal parent, suggesting that one or more of these chromosomes carried a tumor suppressor gene. This has been confirmed by studies showing that the addition of a specific chromosome, chromosome segment, or single gene can suppress the tumorigenic capability of cancer cells. Thus, chromosome 11 suppresses the malignancy of Wilms renal tumor cells and of HeLa or other cervical cancer cells. The gene responsible has been mapped to 11q13, using deletions and translocations (Jesudasan et al., 1995). Another tumor suppressor locus has been mapped to 11p11.2–p12 using microcell hybridization and PCR analysis of a battery of genetic markers scattered along the chromosome (Fig. 28.1; Coleman et al., 1997). The normal function of a tumor suppressor gene is to prevent unregulated growth of cells. When both copies of such a gene are deleted or inactivated by mutation, the absence of the product allows uncontrolled growth to occur. An individual who has inherited a mutant tumor suppressor gene has a greatly increased risk of developing one or more types of cancer, because somatic mutation (deletion or inactivation) of only the single normal copy of the gene is necessary to abolish the tumor-suppressing function of the gene.
KeywordsTumor Suppressor Gene Human Papilloma Virus Imprint Gene Upstream Binding Factor Mutant Tumor Suppressor Gene
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