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DELETION MUTATIONS IN THE HPRT GENE OF T-LYMPHOCYTES AS A BIOMARKER FOR GENOMIC REARRANGEMENTS IMPORTANT IN HUMAN CANCERS
Citation:
Fuscoe, J.C., L. Zimmerman, K. Harrington-Brock, AND M. Moore. DELETION MUTATIONS IN THE HPRT GENE OF T-LYMPHOCYTES AS A BIOMARKER FOR GENOMIC REARRANGEMENTS IMPORTANT IN HUMAN CANCERS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/412.
Description:
The DNA sequence of 11 in vivo-arising intragenic deletion breaksite junctions occurring in the hypoxanthine guanine phosphoribosyltransferase gene of human T-lymphocytes was determined and deletions ranged in size from 16 bp to 4057 bp. o extensive homology was found at the deletion breaksites indicating that nonhomologous recombination was responsible for these deletions. nly one mutation had an unaccounted for nucleotide at the junction. (D)J recombinase recognition sequences, previously identified at other hprt deletion breaksites, were not present. Short regions of homology (1-3 nucleotides) at the deletion termini, which may direct the recombination event, were found in 7 of the mutations. uch features are also found at the deletion and translocation junctions of rearranged oncogenes and suppressor oncogenes. ossible mechanisms include transient misalignment during DNA replication and misjoining of broken DNA strands. The ability to isolate and molecularly analyze mutations occurring in vivo in peripheral human T-lymphocytes allows the assay of DNA breakage/rejoining events. uch a system may serve as a biomarker of exposure to environmental and occupational agents which may be important in the etiology of cancer.