Hyytinen E R, Frierson H F, Sipe T W, Li C L, Degeorges A, Sikes R A, Chung L W, Dong J T
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Prostate. 1999 Nov 1;41(3):190-5. doi: 10.1002/(sici)1097-0045(19991101)41:3<190::aid-pros6>3.0.co;2-2.
Three regions of chromosome 13 were previously identified for having loss of heterozygosity (LOH) in human prostate cancer. One of them, at 13q33, was defined by LOH at markers D13S158 and D13S280. The XPG/ERCC5 gene, 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 in human prostate cancers, in order to determine whether the XPG gene is involved in the development of prostate cancer.
LOH of the XPG gene was analyzed in 40 primary prostate cancers and 14 metastases by using the microsatellite assay, and its mutations were examined in 5 cell lines, 14 metastases, and 8 tumors with LOH at 13q33 by using the single-strand conformation polymorphism (SSCP)-direct DNA sequencing analysis.
Four of the 29 (14%) informative primary tumors and 4 of 8 (50%) metastases 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 revealed 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.
LOH at XPG in prostate cancer supports the conclusion that the 13q33 region contains a gene important in the development of prostate cancer, while lack of mutations of the gene suggests that XPG is not the target gene involved.
先前已确定人类前列腺癌中13号染色体的三个区域存在杂合性缺失（LOH）。其中之一位于13q33，由标记D13S158和D13S280处的LOH定义。XPG/ERCC5基因是一种DNA修复基因，其在种系中发生突变会导致着色性干皮病，该基因已被定位到13q33，位于D13S158和D13S280的一个兆碱基范围内。本文描述了人类前列腺癌中XPG基因的LOH和突变分析，以确定XPG基因是否参与前列腺癌的发生发展。
通过微卫星分析在40例原发性前列腺癌和14例转移癌中分析XPG基因的LOH，并通过单链构象多态性（SSCP）-直接DNA测序分析在5个细胞系、14例转移癌和8例13q33处存在LOH的肿瘤中检测其突变。
29例（14%）信息丰富的原发性肿瘤中有4例，8例（50%）转移癌中有4例显示XPG基因存在LOH。对13q33区域存在LOH的8例肿瘤、14例转移癌和5例前列腺癌细胞系的分析发现了两个多态性，但该基因未发生突变。外显子2中的多态性未改变XPG蛋白的氨基酸序列，但外显子15中的多态性将密码子1104从组氨酸改变为天冬氨酸。这两个多态性也出现在无前列腺癌的个体中。
前列腺癌中XPG基因的LOH支持13q33区域包含一个在前列腺癌发生发展中起重要作用的基因这一结论，而该基因未发生突变表明XPG不是相关的靶基因。
