Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney

The OGG1 gene, which codes for a DNA repair protein with antimutator activity, Is located on chromosome 3p25, a frequent site of allelic deletions in many types of human tumors, including renal clear cell cancers, We present the analysis of 99 renal tumors for alterations in the OGG1 gene to determine its association with tumorigenesis, Loss of heterozygosity in the 3p25 region was found for 85% of the informative cases, We detected somatic missense mutations of the OGG1 gene in 4 of the 99 tumor samples. Biochemical analysis of the mutant proteins revealed that a substitution at codon 46 impairs the enzymatic activity. We also describe the occurrence of several polymorphisms as well as aberrantly spliced OGG1 transcripts.