A comprehensive analysis of loss of heterozygosity caused by hemizygous deletions in renal cell carcinoma using a subtraction library

被引:14
作者
Hatano, N
Nishikawa, NS
McElgunn, C
Sarkar, S
Ozawa, K
Shibanaka, Y
Nakajima, M
Gohiji, K
Kiyama, R
机构
[1] Minist Econ TRade & Ind, Natl Inst Adv Ind Sci & Technol, Inst Mol & Cell Biol, Tsukuba, Ibaraki 3058566, Japan
[2] Novartis Pharma, Tsukuba Res Inst, Ibaraki, Osaka, Japan
[3] Osaka Med Coll, Dept Urol, Osaka, Japan
关键词
renal cell carcinoma; loss of heterozygosity; subtraction library; hemizygous deletion; chromosome; 8;
D O I
10.1002/mc.1051
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Several new loci were identified by a comprehensive analysis of loss of heterozygosity (LOH) using a subtraction library between matched normal and renal cell carcinoma (RCC) tissues. A total of 187 clones from the library, with a Complexity Of 1 x 10(4), were mapped, and 44 clusters of the mapped loci were subjected to LOH analysis using microsatellite markers. A total of 27 loci, which exhibited frequencies of LOH of at least 10% among 44 tumors, mostly clear-cell RCC, included several loci that were reported previously, such as, the von Hippel-Lindau gene, adenomatous polyposis coli, and Interferon regulatory factor-1, as well as new loci, at 5q32-q34, 6q21-q22, 8p12, and others. These loci exhibited LOH among 11.8-93.8% of tumors, and most, If not all, were derived from the sites of hemizyous deletions. The minimum regions of LOH of chromosomes 5, 6, and 8 were 9.0, 10.3, and 0.775 Mb, respectively, The average distance between the cloned fragments on the chromosomes was 2.2 Mb in 187 clones, indicating that the minimum LOH size expected from this subtraction analysis was roughly 50 kb. Therefore, the strategy described here provides comprehensive analysis of LOH sites, which were mostly caused by hemizygous deletions. (C) 2001 Wiley-Liss, Inc.
引用
收藏
页码:161 / 170
页数:10
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