DELETION MUTATIONS IN THE HPRT GENE OF T-LYMPHOCYTES AS A BIOMARKER FOR GENOMIC REARRANGEMENTS IMPORTANT IN HUMAN CANCERS

The DNA sequence of 11 in vivo-arising intragenic deletion junctions o ccurring in the hypoxanthine- guanine phosphoribosyltransferase (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 d eletion breaksites, indicating that non-homologous recombination was r esponsible for these deletions. Short regions of homology (1-3 nucleot ides) at the deletion termini, which may direct the recombination even t, were found in seven of the mutations. Only one mutation had an unac counted for nucleotide at the junction. V(D)J recombinase recognition sequences, previously identified at other hprt deletion breaksites, we re not present. Such features are also found at the deletion and trans location junctions of rearranged oncogenes and suppressor oncogenes. T he ability to isolate and molecularly analyze deletion mutations occur ring 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 importa nt in the etiology of cancer.