Thrash-Bingham C A, Greenberg R E, Howard S, Bruzel A, Bremer M, Goll A, Salazar H, Freed J J, Tartof K D
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2854-8. doi: 10.1073/pnas.92.7.2854.
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.
位于3号染色体短臂上的冯·希佩尔-林道基因座是一种已知与非乳头状肾细胞癌相关的肿瘤抑制基因。先前一项旨在确定肾肿瘤等位基因型的杂合性缺失(LOH)研究表明,除了3号染色体短臂外,5号染色体长臂、6号染色体短臂、10号染色体短臂、11号染色体长臂、17号染色体短臂和19号染色体短臂也可能含有肿瘤抑制基因。然而,细胞遗传学研究显示,在肾肿瘤中,3号染色体短臂、6号染色体短臂、8号染色体短臂、9号染色体短臂和长臂以及14号染色体长臂最常发生核型改变。为了解决这些差异,研究人员使用了一组微卫星DNA探针来扫描杂合性缺失情况,从而使90%的个体肿瘤基因组能够提供有关等位基因缺失的信息。该检测方法也能够检测肿瘤细胞中的定量基因组改变。我们发现,3号染色体短臂的杂合性缺失最为常见。然而,在任何肿瘤中,3号染色体短臂都不是唯一受影响的区域。6号染色体短臂、8号染色体短臂、9号染色体短臂和长臂以及14号染色体长臂的杂合性缺失在非乳头状肿瘤和乳头状肿瘤中也明显增加,这表明两种形式的肾癌病因中涉及的许多肿瘤抑制基因座可能是相同的。