Temporal delineation of sequential HPRT mutations arising in vivo in a T-cell clone with a mutator phenotype.
Recurrent mutations in vivo in T-lymphocytes identify clonally restricted genomic instabilities in some individuals. Cell-based assays allow initial recognition of clones with mutator phenotypes, but genotypic selection is required to determine frequencies and temporal sequences of potentially independent mutational events isolated only as complex changes in the same allele. The present work illustrates how two single-base insertions in the HPRT gene recovered only as a double event in a cell-based assay were shown to arise as separate in vivo mutations, being individually present at frequencies of < or =10(-4) and < or =10(-5), respectively, in peripheral blood. Full characterizations of mutator clones will allow elucidation of the earliest events in the emergence of genomic instability in human somatic cells.
Wilson
V L
VL
Institute of Environmental Studies and the Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. monster77@aol.com
Wade
K R
KR
Yin
X
X
Albertini
R J
RJ
D000328:Adult; D002460:Cell Line; D004247:DNA / Q000097:blood*; D004252:DNA Mutational Analysis / Q000379:methods; D004262:DNA Restriction Enzymes; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes; D013997:Time Factors
D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase; D004262:DNA Restriction Enzymes