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Retinoblastoma gene in malignancy

  • Lance C. Pagliaro
Part of the Cancer Treatment and Research book series (CTAR, volume 84)

Abstract

The central importance of genetic damage in the development of tumors was suspected prior to the advent of molecular biology because chemical carcinogens were noted to be potent mutagens as well [1]. Hereditary cancer syndromes provided further evidence of a genetic basis for carcinogenesis [2]. The identities of the genes involved remained unknown until the 1970s, when the study of animal RNA tumor viruses led to the discovery of several vertebrate genes that could acquire transforming properties through mutation [3,4]. The consequences of these genetic alterations are now beginning to be understood. Knudson proposed that at least two separate mutational events are required, based on his observations of hereditary and nonhereditary retinoblastoma tumors in children [5]. According to his two-hit hypothesis, sporadic tumor formation requires the independent occurrence of both mutations within the same cell, whereas in individuals who inherit one mutation in the germline, only the second mutation is required. Using the estimated frequency of spontaneous mutation, Knudson showed that the hypothesis correctly predicts multiple bilateral tumors in patients with the inherited retinoblastoma susceptibility trait, and solitary unilateral tumors in nonhereditary cases.

Keywords

Retinoblastoma Gene Retinal Progenitor Cell Retinoblastoma Gene Product Acute Myelogenous Leukemia Blast Retinoblastoma Susceptibility Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Kluwer Academic Publishers, Boston 1996

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  • Lance C. Pagliaro

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