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06587-11 Gene Rearrangements as Tumor Specific Markers
EDRI Federal Project Inventory:
06587-11 Gene Rearrangements as Tumor Specific Markers
Sponsor Organization: NIH/CM
Project Title: 06587-11 GENE REARRANGEMENTS AS TUMOR SPECIFIC MARKERS
Project Focus: HUMAN HEALTH EFFECTS
Description: Structural alterations and expression of immunoglobulin (Ig), T-cell
receptor (TCR) and various growth affectinggenes are studies in
normal, "premalignant," and malignant tumors and cell lines. A. We
have shown that hybrid genesare formed by site specific recombination
between variable segments from one immune receptor locus and
joiningsegments from another. We have demonstrated that such events
occur in the peripheral T-cells of all normal individualsbut are 100
times more frequent in the peripheral Tells of patients with ataxia-
telangiectasia (AT). These hybrid genesl) affect and alter the
repertoire of immune receptor diversity, 2) suggest that an underlying
defect in AT may bechromatin "hyperaccessibility," and 3) provide a
possible screening test for people at an increased risk for
thedevelopment of lymphoid specific chromosomal translocations, and
therefore lymphoid malignancy. We have completeda pilot study of
individuals involved in the agriculture industry in which we have
demonstrated an acquired transient "ATlike" picture in individuals
exposed to a variety of pesticides and herbicides. These individuals
are the same populationfor which epidemiological studies have
suggested an increased risk of leukemia and lymphoma. B. We have
developeda murine model of lymphocyte-specific genetic instability and
demonstrated its utility as a predictor of cancer risk as aresult of
certain inherited genes or acquired exposures or both.
References:
Category: MODELS
Subcategory: BASIC RESEARCH
Keywords for Experimental System/Species: HUMAN, MAMMALIAN
Keywords for Experimental Endpoints: EXPOSURE MONITORING, IMMUNOLOGICAL, CARCINOGENESIS
Chemical Agents: PESTICIDES
Performing Institution: NCI INTRAMURAL PROGRAM
Contact: ELAINE C. LEE; BUILDING 31; 11A21, NATIONAL CANCER INSTITUTE,
NIH,BETHESDA, MD 20892-2590; 301- 496-5515; LEEE@OD.NCI.NIH.GOV
