||Deletion Mutations in the hprt Gene of T-Lymphocytes as a Biomarker for Genomic Rearrangements Important in Human Cancers.
Fuscoe, J. C. ;
Zimmerman, L. J. ;
Harrington-Brock, K. ;
Moore, M. M. ;
||Environmental Health Research and Testing, Inc., Research Triangle Park, NC.;Health Effects Research Lab., Research Triangle Park, NC.
Sequence deletion ;
Gene rearrangement ;
Malignant neoplasms ;
Genetic recombination ;
DNA replication ;
Hypoxanthine phosphoribosyltransferase ;
Biological markers ;
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The DNA sequence of 11 in vivo-arising intragenic deletion junctions occurring in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene of human T-lymphocytes was determined. These delections ranged in size from 16 bp to 4057 bp. Extensive homology was not found at the deletion breaksites, indicating that non-homologous recombination was responsible for these deletions. Short regions of homology (1-3 nucleotides) at the deletion termini, which may direct the recombination event, were found in seven of the mutations. Only one mutation had an unaccounted for nucleotide at the junction. V(D)J recombinase recognition sequences, previously identified at other hprt deletion breaksites, were not present. Such features are also found at the deletion and translocation junctions of rearranged oncogenes and suppressor oncogenes. The ability to isolate and molecularly analyze deletion mutations occurring in vivo in peripheral human T-lymphocytes allows the assay of DNA breakage/rejoining events.