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  • Title: Characteristic loss of heterozygosity in chromosome 3P and low frequency of replication errors in sporadic renal cell carcinoma.
    Author: Chino K, Esumi M, Ishida H, Okada K.
    Journal: J Urol; 1999 Aug; 162(2):614-8. PubMed ID: 10411097.
    Abstract:
    PURPOSE: A high frequency of genetic loss at 4 loci on chromosome 3p has been shown in human sporadic renal cell carcinomas (RCCs), but the relative contribution of each locus is not well known, and the involvement of DNA replication errors (RERs) in carcinogenesis of RCCs remains unclear. We report the simultaneous comparison of genetic loss at the 4 chromosome 3p loci and RERs in sporadic RCCs. MATERIALS AND METHODS: DNA was extracted from 33 Japanese sporadic RCC samples, and examined for loss of heterozygosity (LOH) and RERs by amplification of 14 microsatellite regions. LOH of the von Hippel Lindau (VHL) gene was analyzed by a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. The target sequences of RER, transforming growth factor beta type II receptor (TGFbetaRII) and Bcl-2-associated X protein (BAX) genes were amplified and analyzed for mutations by sequencing. RESULTS: LOH of the VHL gene was observed in 53.3% of RCCs, a higher frequency than that of the 4 regions 3p12-p13 (18.8%), 3p14.2 (17.4%), 3p21 (21.2%) and 3p25-p26 except for VHL (31.3%). There were no RERs in 14 microsatellite regions, including the mononucleotide (A)10 repeats of the TGFbetaRII gene and (G)8 repeats of the BAX gene. CONCLUSION: Japanese sporadic RCCs were characterized by predominant loss of VHL gene and low contribution of the other 3 candidate RCC tumor suppressor genes. RERs, mostly caused by a defect of DNA mismatch repair, might only rarely be involved in the carcinogenesis of sporadic RCCs.
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