title: The unexpected landscape of in vivo somatic mutation in a human epithelial cell lineage.
abstract: Few data exist on somatic mutation in the epithelial cell lineages that play a central role in human biology and disease. To delineate the "landscape" of somatic mutation in a human epithelial cell lineage, we determined the frequency and molecular nature of somatic mutations occurring in vivo in the X-linked HPRT gene of kidney tubular epithelial cells. Kidney epithelial mutants were frequent (range 0.5 to 4.2 x 10(-4)) and contained a high proportion of unreported HPRT base substitutions, -1-bp deletions and multiple mutations. This spectrum of somatic mutation differed from HPRT mutations identified in human peripheral blood T lymphocytes and from germ-line HPRT mutations identified in Lesch-Nyhan syndrome or hyperuricemia patients. Our results indicate that DNA damage and mutagenesis may have unusual or mechanistically interesting features in kidney tubular epithelium, and that somatic mutation may play a more important role in human kidney disease than has been previously appreciated.
authors.affiliation: Department of Pathology, University of Washington, Box 357705, Seattle, WA 98195-7705, USA.
authors.forename: Lorel M
authors.initials: LM
authors.lastname: Colgin
authors.forename: Alden F M
authors.initials: AF
authors.lastname: Hackmann
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Emond
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Monnat
mesh_terms: D002478:Cells, Cultured; D002999:Clone Cells; D004251:DNA Transposable Elements; D005091:Exons; D005784:Gene Amplification; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007684:Kidney Tubules; D009154:Mutation; D020125:Mutation, Missense; D016366:Open Reading Frames; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000201:enzymology; D013866:Thioguanine / Q000494:pharmacology*; D019459:Urothelium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
chemical_list: D004251:DNA Transposable Elements; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine