A loss of genetic information has been postulated to play a key role in the development of human cancer. This concept has been supported by several types of investigations. Somatic cell hybrids between tumorigenic human cancer cells and their normal cellular counterparts are totally suppressed for tumor-forming ability indicating that tumorigenicity behaves as a recessive genetic trait. Furthermore specific chromosomal deletions have been identified in certain types of pediatric cancers implying the loss of certain critical genes during development of these tumors. Despite this strong circumstantial evidence for the existence of recessive cancer genes, little is known about the functions, number or locations of these genes. One appraoch to characterizing these recessive cancer genes is to study whole cell hybrids between different pediatric tumor cells and microcell hybrids into which normal human chromosomes have been introduced. A complementation analysis using whole cell hybrids would determine how many different cancer genes are invoved in the development of human cancer. The location of these genes can be revealed by the introductin of individual chromosomes into pediatric cancer cells. Further localization of the sites of these genes can be accomplished by the use of chromosomal transloations and RFLP analyses. The hybrid cell will also be characterized for in vitro growth parameters associated with transformation including serum growth factor requirements, anchorage independent growth, fibronectin expression and production of plasminogen activator. Tumorigenic potential will be assayed by the injection of these cells into nu/nu mice. Cellular protein synthesis will be characterized by two- dimensional polyacrylamide electrophoresis. These studies will provide new insights into the functions of recessive cancer genes in human cells and serve as the basis for future molecular cloning studies.
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