Title: The unexpected landscape of in vivo somatic mutation in a human epithelial cell lineage.

Authors: Colgin, Lorel M; Hackmann, Alden F M; Emond, Mary J; Monnat Jr, Raymond J

Published In Proc Natl Acad Sci U S A, (2002 Feb 05)

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.

PubMed ID: 11818556

MeSH Terms: Cells, Cultured; Clone Cells; DNA Transposable Elements; Exons; Gene Amplification; Humans; Hypoxanthine Phosphoribosyltransferase/genetics*; Kidney Tubules; Mutation*; Mutation, Missense; Open Reading Frames; Reverse Transcriptase Polymerase Chain Reaction; Sequence Deletion; T-Lymphocytes/enzymology; Thioguanine/pharmacology*; Urothelium/cytology; Urothelium/drug effects; Urothelium/enzymology*