BREAKPOINTS AND JUNCTIONAL REGIONS OF INTRAGENIC DELETIONS IN THE HPRT GENE IN HUMAN T-CELLS

DNA sequences of the deletion breakpoints of 24 human T-lymphocyte hpr t gene mutations are reported. These independent deletions ranged in s ize from 18 to 15655 base pairs. Seven of the 21 in vivo mutations aro se in normal adults, three in normal children, eight in radioimmunothe rapy patients and three in platinum chemotherapy patients. One in vitr o mutation was isolated after 93cGy radon exposure and two after 300cG y gamma radiation. The breakpoints were found to be non-random and a c luster of small deletions in exon 6 is reported. Ten of the mutations had 2-5bp direct repeats at the breakpoints. There was no excess of '' deletion-associated'' motifs over that expected by chance. Some breakp oints do occur at consensus topoisomerase II cleavage sites and the ce ntromeric end of a Donehower sequence occurs exactly at a telomeric br eakpoint. Three mutants had breakpoints at hairpins expected by tile m odel of Glickman and Ripley (1).