Genome imprinting and cancer genetics.
Parent-of-origin-dependent modification of the genome (genome imprinting) is thought to be involved in the formation of several types of human cancer. Simple modifications of Knudson's two-hit model give rise to two types of predictions with respect to the genetic behavior of such diseases. In the first, rare alleles of modifier genes will give rise to the retention of the same parent's tumor suppressor alleles in sporadic cases. In the second, other variants of the modifier genes will result in failure to establish linkage between tumor suppressor genes and disease predisposition in familial cases. Both of these predictions are fulfilled by experiment. Additional modifications of existing models are predicted to result in more complex patterns of inheritance. The demonstration of such patterns in human pedigrees will require an extremely sophisticated level of genetic analysis.
Sapienza
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Ludwig Institute for Cancer Research, Department of Medicine, University of California, San Diego, La Jolla 92093-0660.
D015894:Genome, Human; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D010063:Ovum / Q000502:physiology*; D010641:Phenotype; D013094:Spermatozoa / Q000502:physiology*