There are two aspects of this Core. In the first we will exploit a newly developed procedure to make chromosome-specific and chromosome region- specific probes for fluorescent in-situ hybridization. The new procedure, based on inter-Alu-PCR of DNA from hybrid cells containing localized regions of the human genome results in probe specific for painting those regions of the genome in human normal and cancer cells. Probes will be made for the various candidate regions of the human genome implicated in human pediatric cancer. This methodology will then be combined with a new approach for making direct cytogenetic preparations from pediatric tumors, and tumors cultured in nude mice, in order to investigate primary chromosomal events associated with those cancers. Probes will also be applied to tumor cell lines derived from Li-Fraumeni patients and families to once again identify non-random chromosomal changes associated with that syndrome. Pediatric cancer patients presenting with congenital abnormalities will have their lymphocytes studied by traditional G-band cytogenetics in order to identify candidate regions for further analyses. For any chromosomal regions so identified, painting probe will be produced as above for in depth analysis and confirmation of the suspected chromosomal abnormalities. The second aspect of the Core is to provide isozyme genetic signature analysis on tumors grown in nude mice to rapidly and unambiguously verify their human origin. To a lesser extent this aspect of the Core will also help verify the genetic origin of cell lines and nude mouse tumors developed from pediatric cancer patients.
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