A novel signature mutation for oxidative damage resembles a mutational pattern found commonly in human cancers

• Published in: Cancer research (Chicago, Ill.) Vol. 59; no. 8; pp. 1837 - 1839
• Main Authors: TURKER, M. S, GAGE, B. M, ROSE, J. A, ELROY, D, PONOMAREVA, O. N, STAMBROOK, P. J, TISCHFIELD, J. A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-04-1999
• Subjects: Adenine Phosphoribosyltransferase - genetics; Animals; Biological and medical sciences; Cell metabolism, cell oxidation; Cell physiology; Cells, Cultured; Chromosomes, Human, Pair 8; DNA Damage - genetics; Female; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen Peroxide - pharmacology; Kidney - cytology; Loss of Heterozygosity; Male; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Mutation - drug effects; Neoplasms - genetics; Oxidative Stress - genetics; Human; Oxidative stress; Enzyme; Transferases; Glycosyltransferases; Rodentia; Hydroperoxide; Malignant tumor; Kidney; Vertebrata; Mammalia; Mouse; Animal; Established cell line; Loss of heterozygosity; Mutation; Adenine phosphoribosyltransferase; Pentosyltransferases
• ISSN: 0008-5472; 1538-7445

To determine the types of mutations induced by oxidative damage, a kidney cell line with a heterozygous deficiency for the autosomal Aprt (adenine phosphoribosyltransferase) gene was tested for its mutagenic response to hydrogen peroxide. Aprt-deficient cells were selected and scored for loss of heterozygosity (LOH) for 11 microsatellite loci on mouse chromosome 8. On the basis of the LOH analysis, spontaneous mutants (n = 38) were distributed into four classes: apparent point mutation, mitotic recombination, chromosome loss, and large interstitial deletion. However, 9 of 20 (45%) hydrogen peroxide-induced mutants exhibited a novel class of mutations characterized by "discontinuous LOH" for one or more of the microsatellite loci. Interestingly, mutations resembling discontinuous LOH are commonly observed in a wide variety of human cancers. Our data suggest that discontinuous LOH is a signature mutational pattern for oxidative damage and further suggest that such genetic damage is widespread in cancer.