© 1994 Oxford University Press
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Deletion mutations in the hprt gene of T-lymphocytes as a biomarker for genomic rearrangements important in human cancers
1Environmental Health Research and Testing, Inc. PO Box 12199, Research Triangle Park, NC 27709
2Genetic Toxicology Division, Health Effects Research Laboratory, US Environmental Protection Agency Research Triangle Park, NC 27710, USA
3Present address: Integrated Laboratory Systems, PO Box 13501, Research Triangle Park, NC 27709, USA
4To whom requests for reprints should be addressed at his present address
The DNA sequence of 11 in vivo-arising intragenic deletion junctions occurring in the hypoxanthine-guanine phospho-ribosyltransferase (hprt) gene of human T-lymphocytes was determined. These deletions 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 deletiontermini, 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 junctionsof 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. Such a system may serve as a biomarker of exposure to environmental and occupational agents which may be important in the etiology of cancer.