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人类卵巢癌中6号染色体长臂、11号和17号染色体上杂合性的频繁缺失。

Frequent loss of heterozygosity on chromosomes 6q, 11, and 17 in human ovarian carcinomas.

作者信息

Lee J H, Kavanagh J J, Wildrick D M, Wharton J T, Blick M

机构信息

Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.

出版信息

Cancer Res. 1990 May 1;50(9):2724-8.

PMID:2328498
Abstract

Recently, tumor-specific allele loss has been shown to be an important characteristic of some tumors. When such loss includes one or more growth-regulatory genes, it may allow the expression of tumorigenicity. Using Southern blots, we analyzed normal and tumor DNA samples from 19 ovarian cancer patients, using a series of polymorphic DNA probes that map to a variety of chromosomal loci. Of 14 informative cases, tumor-specific allelic loss was observed in nine (64%) at the estrogen receptor (ESR) gene locus on chromosome 6q. On chromosome 17p at the D17S28 and D17S30 loci, allelic losses were also detected in 6 of 8 (75%) and 9 of 14 (64%) cases, respectively. Allelic loss at the HRAS1 gene locus on chromosome 11p occurred in 5 of 11 (46%) informative cases. The relatively high incidence of these allelic losses observed on chromosome 6q represents the first implication by molecular genetic analysis of this chromosomal region in a human malignancy, and it thus appears to be a genetic change specific to ovarian carcinoma. DNA sequence losses on 11p and 17p, also reported for other cancers, may reflect the presence of tumor- or growth-suppressor genes on these chromosomes that are important in the genesis of many tumor types, including ovarian malignancies.

摘要

最近,肿瘤特异性等位基因缺失已被证明是某些肿瘤的一个重要特征。当这种缺失包括一个或多个生长调节基因时,可能会导致致瘤性的表达。我们使用Southern印迹法,利用一系列定位到各种染色体位点的多态性DNA探针,分析了19例卵巢癌患者的正常和肿瘤DNA样本。在14例信息丰富的病例中,9例(64%)在6号染色体q臂上的雌激素受体(ESR)基因位点观察到肿瘤特异性等位基因缺失。在17号染色体p臂上的D17S28和D17S30位点,分别在8例中的6例(75%)和14例中的9例(64%)检测到等位基因缺失。在11号染色体p臂上的HRAS1基因位点,11例信息丰富的病例中有5例(46%)发生等位基因缺失。在6号染色体q臂上观察到的这些等位基因缺失的相对高发生率,是分子遗传学分析首次表明该染色体区域在人类恶性肿瘤中的作用,因此似乎是卵巢癌特有的基因变化。11号染色体p臂和17号染色体p臂上的DNA序列缺失,在其他癌症中也有报道,可能反映了这些染色体上存在对包括卵巢恶性肿瘤在内的许多肿瘤类型发生重要作用的肿瘤抑制基因或生长抑制基因。

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