The purpose of this research is to evaluate the applicability of recombinant DNA technology and molecular genetic analysis to the clinical diagnosis and detection of cancer in children. The utilization of cloned human DNA segments in defining unique molecular changes in the arrangement or number of loci which occur in malignant cells as compared to normal cells from the same patients may serve as an exquisitely sensitive measure of the type of existing cancer and its expected prognosis. The establishment of a large resource panel of paired normal and neoplastic samples will be of primary importance. The interaction of pediatric oncologists and pathologists based in hospitals which are members of the Children's Cancer Study Group (CCSG) will allow access to several hundred new tumors a year. Each of the pathologic, clinical and laboratory evaluations of these cases are routinely reviewed by the CCSG using standardized criteria and protocols. Thus, over a thousand well-defined primary samples will be available for analysis. Additional materials from these samples will be generated by Epstein-Barr virus transformation of peripheral blood lymphocytes from each case and by passaging most solid tumors in immunodeficient mice, thereby assuring continued viability of this resource. Paired normal and neoplastic sample sets will be processed for DNA isolation and analyzed for two different, but complementary, molecular features. Hybridization of these DNA samples with cellular and viral oncogene probes will allow detection of somatic tumor-specific amplifications or rearrrangement of genomic loci homologous to these probes. Examination of many tumors of each specific pathologic type may then allow insight into the association of these events with the development of such cancers. Similar evaluations of patients following therapy or in relapse may also provide prognostic information of particular use to the clinical oncologist. The sets of samples of each of the various types will be examined with hybridization probes consisting of segments of genomic human DNA which are homologous to chromosomal loci encompassing polymorphic restriction endonuclease recognition sequences. Comparison of genotypes present in normal and malignant tissues at loci throughout the genome may allow identification of genes whose recessive alleles predispose to specific cancers. (6)
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