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Antioncogenes and human cancer
1Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111.
Abstract:
The antioncogenes, or tumor suppressor genes, as negative regulators of cell division, stand in contrast to oncogenes. For most human cancers, the more frequently mutated genes are the antioncogenes, the principal exception being the leukemias and lymphomas. Persons heterozygous for germ-line mutations in antioncogenes are strongly predisposed to one or more kinds of cancer, and most dominantly inherited cancer is attributable to such heterozygosity. Seven antioncogenes have been cloned through the study of these persons, and several others have been mapped. An eighth one was mapped and cloned through the investigation of tumors and is not yet known in hereditary form. Three dominantly inherited forms of cancer are not attributable to mutations in antioncogenes. The corresponding nonhereditary forms of most cancers generally reveal abnormalities of the same antioncogenes that are found in the hereditary forms but may also show additional ones. Some cancers, especially the embryonal tumors of children, have a small number of antioncogene mutations; some others, such as most sarcomas, have more, and the common carcinomas have the most, reflecting a hierarchy of controls over growth of stem cell populations. Still more members of this gene category remain to be mapped and cloned through the study of cancer families and of tumors. The genes that have been cloned act at diverse points in the signal transduction pathway in cells, from the outer cell membranes to sites of gene transcription, in some cases as negative regulators of oncogene expression.
Insights
Antioncogenes, or tumor suppressor genes, are frequently mutated in most human cancers and predispose individuals to cancer when mutated in the germline. Further research is needed to map and clone additional antioncogenes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Antioncogenes (tumor suppressor genes) function as negative regulators of cell division, contrasting with oncogenes.
- Mutations in antioncogenes are prevalent in most human cancers, with exceptions like leukemias and lymphomas.
- Germline heterozygosity for antioncogene mutations strongly predisposes individuals to hereditary cancers.
Purpose of the Study:
- To review the role of antioncogenes in cancer development.
- To highlight the cloning and mapping of identified antioncogenes.
- To discuss the varying mutation frequencies of antioncogenes across different cancer types.
Main Methods:
- Cloning and mapping of antioncogenes through studies of hereditary cancer families and tumor investigations.
- Analysis of antioncogene abnormalities in both hereditary and nonhereditary cancer forms.
- Comparison of antioncogene mutation frequencies across diverse cancer types.
Main Results:
- Seven antioncogenes have been cloned from studies of individuals with hereditary cancer.
- An eighth antioncogene was mapped and cloned via tumor investigation.
- Hereditary cancers are often linked to antioncogene heterozygosity, while nonhereditary cancers may show similar or additional antioncogene abnormalities.
Conclusions:
- Antioncogenes play a critical role in regulating cell division and preventing cancer.
- Further identification and characterization of antioncogenes are essential for understanding cancer etiology.
- Antioncogene functions span various cellular pathways, including signal transduction and gene expression regulation.