Association of a specific chromosomal abnormality with a specific tumor type is well established and may reflect mechanisms of oncogenesis peculiar to that tumor. Alternatively, it may be that these association reflect that particular differentiated state of the malignant cell, consistent with the model that rearrangements occur within chromatin in an """"""""active"""""""" configuration. Using this concept as a predictive and testable hypothesis, we are investigating the relationship of specific chromosomal abnormalities to certain tumors. Our focus at present is on diseases of the hematopoietic system. This research program requires expertise in a number of distinct biological techniques. We have established this technical expertise which includes 1) our capability to grow and maintain a wide array of primary cells and cell lines, 2) our facility is doing basic cytogenetic analyses, as well as the more involved procedure of chromosome in situ hybridization, and 3) our constantly updated ability to utilize the very newest of molecular biological techniques to clone, map, sequence, and perform expression studies on DNA segments of interest. We previously demonstrated that in a T cell and B cell tumor with a particular chromosomal abnormality (inv 14) we could account for the occurrence of the inversion by a site-specific recombination event between the Ig and TCR loci despite the fact that these loci are felt to be distinct and disparately activated. One measure of """"""""accessibility"""""""" of genomic DNA is to analyze transcriptional activity derived from it. Perhaps, a naive view, but one that we will propose for the sake of this argument, is that if DNA is accessible to a RNA polymerase it might very well be accessible to a recombinase. We, therefore, surveyed T cell tumors and normal polyclonal T-cell populations for evidence of immunoglobulin heavy chain variable region transcription. Contrary to models of distinct T cell/B cell lineage divergence, we found evidence for immunoglobulin heavy chain variable regions transcription in T cells. This finding speaks to important issues in lymphocyte development and may have relevance to the occurrence of cancer in these cells as well.

National Institute of Health (NIH)
Division of Cancer Treatment (NCI)
Intramural Research (Z01)
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Cancer Treatment
United States
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