PURPOSE: Genomic instability of microsatellite in patients with defects in the mismatch repair system of DNA resulting in replication error (RER) has a high risk of accumulating mutations in oncogene and tumor suppressor gene. In this study, we evaluated the incidence of microsatellite instability (MI) in renal cell carcinoma (RCC) by comparing polymerase chain reaction (PCR)-amplified sequences from frozen samples of normal and tumor tissue from affected patients. MATERIALS AND METHODS: Analysis of MI using the PCR based assay was performed in total 25 cases of RCC, including 21 clear cell types and 4 papillary types. MI of tumor DNA was observed as the occurrence of additional or absence of constitutional autoradiographic signals, or as at least a two to threefold increase or decrease of intensity of the autographic signals in comparison to the corresponding normal tissue DNA. Total 11 microsatellite loci were studied; 4 loci at 3p (D3S1274, D3S1296, D3S1300, D3S1313), 3 loci at 9p (IFNA, D9S1747, D9S171) and 4 loci at 17p (D17S513, D17S695, TP53, D17S261). RESULTS: Twenty-one of 25 RCC (84%) displayed MI in at least one informative locus. MI was found in 15 of 25 cases (60%) at 3p region and 7 of 25 cases (28%) at 9p region. All of them were clear cell type of RCC. MI was detected in 11 cases (44%) at 17p region, 7 of them were clear cell type. In all 4 cases of papillary type, MI was observed only at 17p region. CONCLUSIONS: These results suggest that alterations of 3p region might occur in the early stage of tumorigenesis in RCC. The DNA mismatch repair system may play an important role in tumorigenesis of RCC and MI analysis could be a useful method to detect early genetic alterations in RCC. Genetic alterations in tumorigenesis of RCC may have some differences according to the histologic characteristics.
Carcinogenesis ; Carcinoma, Renal Cell* ; DNA ; DNA Mismatch Repair ; Genes, Tumor Suppressor ; Genomic Instability ; Humans ; Incidence ; Microsatellite Instability ; Microsatellite Repeats* ; Oncogenes ; Polymerase Chain Reaction