Somatic mutations are frequent and increase with age in human kidney epithelial cells

Hum Mol Genet. 1996 Feb;5(2):215-21. doi: 10.1093/hmg/5.2.215.


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 approximately 5 x 10(-5) for donors in the first decade of life to approximately 2.5 x 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 nephrectomy 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging*
  • Base Sequence
  • Carcinoma / physiopathology
  • Cells, Cultured
  • Child
  • Child, Preschool
  • DNA Primers
  • Epithelium
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / deficiency
  • Hypoxanthine Phosphoribosyltransferase / genetics*
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / physiology
  • Kidney Cortex / cytology
  • Kidney Cortex / drug effects
  • Kidney Cortex / pathology
  • Kidney Cortex / physiology*
  • Kidney Neoplasms / physiopathology
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Nephrectomy
  • Thioguanine / pharmacology*


  • DNA Primers
  • Hypoxanthine Phosphoribosyltransferase
  • Thioguanine