Loss of heterozygosity and lack of mutations of the XPG/ERCC5 DNA repair gene at 13q33 in prostate cancer

BACKGROUND. Three regions of chromosome 13 were previously identified for h aving loss of heterozygosity (LOH) in human prostate cancer. One of them, a t 13q33, was defined by LOH at markers D13S158 and D13S280. The XPG/ERCC5 g ene, a DNA repair gene that when mutated in the germline leads to xeroderma pigmentosum, has been mapped to 13q33, within one megabase of D13S158 and D13S280. This paper describes LOH and mutational analysis of the XPG gene i n human prostate cancers, in order to determine whether the XPG gene is inv olved in the development of prostate cancer. METHODS. LOH of the XPG gene was analyzed in 40 primary prostate cancers an d 14 metastases by using the microsatellite assay, and its mutations were e xamined in 5 cell lines, 14 metastases, and 8 tumors with LOH at 13q33 by u sing the single-strand conformation polymorphism (SSCP)-direct DNA sequenci ng analysis. RESULTS. Four of the 29 (14%) informative primary tumors and 4 of 8 (50%) m etastases showed LOH for the XPG gene. Analysis of the 8 tumors with LOH at the 13q33 region, 14 metastases, and 5 cell lines of prostate cancer revea led two polymorphisms but no mutation of the gene. The polymorphism in exon 2 did not change the amino-acid sequence of the XPG protein, but the exon 15 polymorphism altered codon 1104 from histidine to aspartic acid. The two polymorphisms also occurred in individuals without prostate cancer. CONCLUSIONS. LOH at XPG in prostate cancer supports the conclusion that the 13q33 region contains a gene important in the development of prostate canc er, while lack of mutations of the gene suggests that XPG is not the target gene involved. (C) 1999 Wiley-Liss, Inc.