Temporal delineation of sequential HPRT mutations arising in vivo in a T-cell clone with a mutator phenotype

Document Type

Article

Publication Date

2-20-2001

Abstract

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 ≤10-4 and ≤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. © 2001 Elsevier Science B.V.

Publication Source (Journal or Book title)

Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis

First Page

181

Last Page

199

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