GENETIC INSTABILITY IN HUMAN T-LYMPHOCYTES

Mutations arising in vivo in the hypoxanthine-guanine phosphoribosyltr ansferase (HPRT) gene of T-lymphocytes provide a measure of mutation i nduction in human somatic cells. Studies of measured background HPRT m utant frequency (MF) values show wide inter-individual variation. At t he extremes are individuals with 'outlier' MF values, i.e., non-expose d individuals with MF > 100 X 10(-6) [Robinson et al., Mutation Res. 3 13 (1994) 227-247.]. The elevated HPRT MF in one well-studied outlier is due to the in vivo expansion of mutant cells possessing an identica l T-cell receptor (TCR) gene rearrangement pattern. We report here tha t this in vivo expanding TCR clone shows multiple different HPRT mutat ions and thus possesses a mutator phenotype. Other individuals with T- cell mutator phenotypes have been found, suggesting that this phenomen on may contribute to the extremes of variation in HPRT MFs in the huma n population. (C) 1998 Elsevier Science B,V. All rights reserved.