Our long-term research goal is to understand the role played by chromosome changes in the etiology and clinical behavior of human tumors. Recently, there has been intense activity in the cytogenetic and molecular biological investigations of chromosome abnormality in tumor cells, especially those that arise in the lympho-hematopoietic system. This was catalyzed by two developments: (1) the conclusion from the currently available extensive tumor cytogenetic data that several chromosome changes in tumor cells are specific enough to serve as independent diagnostic and prognostic factors and (b) the availability of atleast one major model of gene activation mediated by chromosome rearrangement, namely, the activation of c-myc in B cell neoplasia consequent upon its translocation into the Ig gene loci. Inspite of these exciting developments much remains unknown about the significance of chromosome change to the initiation, evolution, and clinical behavior of tumors that arise in the lympho-hematopoietic system and elsewhere. In this application, we propose to continue our ongoing studies of chromosome changes, especially rearrangements in leukemia and lymphoma in order to further define the specificity of these changes in relation to histologic subtypes and defined tumor etiologies, continue to map the chromosomal sites of genes that are relavent to tumorigenesis and to correlate their positions and movements with break points or rearrangement, analyze the break points at the molecular level, and identify and clone novel gene sequences that translocate into genes such as the Ig, T cell receptor, and cellular oncogenes. These studies, we feel, will permit new insights into the origin and significance of gene and chromosome instability in the development of leukemia and lymphoma. We will use molecular techniques in conjunction with cytogenetic methods to better define the relationship between gene and chromosome rearrangements and tumor histology on the one hand and clinical features of patients such as remission and response to treatment on the other. The patient population for these studies will comprise adult and childhood leukemia and lymphoma patients entered on MSKCC treatment protocols. Methods for these studies (extended banding cytogenetics, recombinant DNA assays, and biostatistical analysis) are well developed in our laboratory.
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