caa a22 4500 397574452 CHVBK 20180308164851.0 cr unu---uuuuu 161202e199602 xx s 000 0 eng 10.1093/hmg/5.2.215 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.2.215 Somatic Mutations Are Frequent and Increase with Age in Human Kidney Epithelial Cells [Elektronische Daten] [George M. Martin, Charles E. Ogburn, Lorel M. Colgin, Allen M. Gown, Steven D. Edland, Raymond J. Monnat] We have used a primary cloning assay to determine the frequency of 6-thioguanine (TG)-resistant tubular epithelial cells in kidney tissue from 72 human donors ranging in age from 2 to 94 years. The frequency of TG-resistant mutants ranged from ∼5 × 10−5 for donors in the first decade of life to ∼2.5 × 10−4 for donors in the eighth and later decades of life. Two different statistical analyses indicated that this increase in mutant frequency is exponential with age. We also observed a 2-fold higher TG-resistant mutant frequency in neph-rectomy kidneys containing a coincident renal carcinoma. DNA sequence analyses revealed HPRT gene mutations in each of 14 TG-resistant mutants from seven unrelated donors. Thirteen of these 14 mutants resulted from independent mutational events. These results suggest that somatic mutations are common in renal—and perhaps in other human—epithelia, and thus could play an important role in the genesis of age-associated disease. © 1996 Oxford University Press Martin George M. Department of Pathology, University of Washington, Seattle, WA 98195, USA aut Ogburn Charles E. Department of Pathology, University of Washington, Seattle, WA 98195, USA aut Colgin Lorel M. Department of Pathology, University of Washington, Seattle, WA 98195, USA aut Gown Allen M. Department of Pathology, University of Washington, Seattle, WA 98195, USA aut Edland Steven D. Department of Biostatistics, University of Washington, Seattle, WA 98195, USA aut Monnat Raymond J. Department of Pathology, University of Washington, Seattle, WA 98195, USA aut Human Molecular Genetics Oxford University Press 5/2(1996-02), 215-221 0964-6906 5:2<215 1996 5 hmg https://doi.org/10.1093/hmg/5.2.215 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.2.215 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Martin George M. Department of Pathology, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Ogburn Charles E. Department of Pathology, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Colgin Lorel M. Department of Pathology, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Gown Allen M. Department of Pathology, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Edland Steven D. Department of Biostatistics, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Monnat Raymond J. Department of Pathology, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/2(1996-02), 215-221 0964-6906 5:2<215 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford