Comprehensive allelotyping of human renal cell carcinomas using microsatellite DNA probes.

The von Hippel-Lindau locus on chromosome 3p is a tumor suppressor gene known to be involved in nonpapillary renal cell carcinoma. A previous loss of heterozygosity (LOH) study aimed at determining the allelotype of kidney tumors has indicated that in addition to 3p, chromosome arms 5q, 6q, 10q, 11q, 17p, and 19p may also harbor tumor suppressor genes. However, cytogenetic studies reveal that chromosomes 3p, 6q, 8p, 9pq, and 14q most frequently undergo karyotypic changes in renal tumors. To resolve these differences, a collection of microsatellite DNA probes has been used to scan for LOH so that 90% of individual tumor genomes were rendered informative for allele loss. The assay is capable of detecting quantitative genomic alterations in tumor cells as well. We find that LOH is most frequent for chromosome arm 3p. However, in no tumor is 3p exclusively affected. LOH for 6q, 8p, 9pq, and 14q is also distinctly elevated for both nonpapillary as well as papillary tumors and suggest that many of the tumor suppressor loci involved may be common to the etiology of both forms of kidney cancer. IMAGES:

3号染色体短臂（3p）上的希佩尔-林道（von Hippel-Lindau）位点是一类抑癌基因，现已证实其参与非乳头状肾细胞癌的发生发展。此前一项旨在解析肾脏肿瘤等位基因谱的杂合性缺失（loss of heterozygosity, LOH）研究表明，除3p外，5q、6q、10q、11q、17p及19p染色体臂也可能携带有抑癌基因。但细胞遗传学研究显示，肾肿瘤中最常发生核型改变的染色体区域为3p、6q、8p、9pq与14q。为厘清上述研究结论间的分歧，本研究采用微卫星DNA探针（microsatellite DNA probes）集扫描杂合性缺失事件，最终使90%的个体肿瘤基因组可获得等位基因缺失检测所需的有效信息。该检测手段同样可检出肿瘤细胞的定量基因组变异。本研究发现，3p染色体臂的杂合性缺失发生率最高，但未发现仅存在3p缺失的肾肿瘤。6q、8p、9pq及14q的杂合性缺失在非乳头状与乳头状肾肿瘤中均显著升高，提示两类肾癌的致病机制可能共享多个相关抑癌基因位点。IMAGES: