Allelotype of human malignant astrocytoma.
Allelotype of human malignant astrocytoma.
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发表时间：
1990-09
期刊：
影响因子：
11.2
通讯作者：
D. Fults;C. Pedone;G. A. Thomas;Ray White;Ray White
中科院分区：
文献类型：
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作者：
D. Fults;C. Pedone;G. A. Thomas;Ray White;Ray White
星形细胞瘤是人类最常见的脑瘤，通常是恶性的，几乎无法治愈。恶性星形细胞瘤有两种类型：间变性星形细胞瘤和多形性胶质母细胞瘤。利用DNA标记检测限制性片段长度多态性的研究表明，在恶性星形细胞瘤患者的肿瘤DNA中，第10号和17P号染色体上的座位经常丢失，这表明在星形细胞瘤发生中起重要作用的抑癌基因可能存在于两条不同的染色体上。为了确定更多的染色体丢失区域，我们对41例恶性星形细胞瘤患者进行了等位基因分析，对每个常染色体的每条臂使用了限制性片段长度多态标记。除了21号染色体外，所有常染色体都发现了杂合性丢失，这表明基因组变化的复杂性比以前报道的更大。许多肿瘤表现为多条染色体杂合性缺失，涉及的染色体数目与肿瘤组织病理学相关。对这些患者的10号染色体的高分辨限制性片段长度多态性研究表明，10号染色体大范围区域的丢失是一种常见的事件，特别是在多形性胶质母细胞瘤中。只对另一种肿瘤--人结直肠癌进行了等位基因分析。在恶性星形细胞瘤和结直肠癌中观察到不同的等位基因丢失情况，提示导致这两种人类癌症的基因事件可能沿着不同的途径进行。
Astrocytoma, the most common brain tumor in humans, is usually malignant and virtually incurable. Two types of malignant astrocytomas can be distinguished histopathologically: anaplastic astrocytoma and glioblastoma multiforme. Studies using DNA markers that detect restriction fragment length polymorphisms have shown that loci on chromosomes 10 and 17p are lost frequently in tumor DNA from malignant astrocytoma patients, suggesting that tumor suppressor genes important in astrocytoma tumorigenesis may be present on 2 different chromosomes. To identify additional regions of chromosome loss, we carried out an allelotype analysis of 41 malignant astrocytoma patients using restriction fragment length polymorphism markers for each arm of every human autosome. Loss of heterozygosity was found for every autosome except chromosome 21, indicating an even greater complexity of genomic alterations than reported previously. Many tumors showed loss of heterozygosity for multiple chromosomes and the number of chromosomes involved correlated with tumor histopathology. A high-resolution restriction fragment length polymorphism study of chromosome 10 loci in these patients showed that loss of broad regions of chromosome 10 was a common event, particularly in glioblastoma multiforme. An allelotype analysis has been carried out on only one other tumor, human colorectal carcinoma. Different profiles of allele loss were observed in malignant astrocytoma and colorectal carcinoma, suggesting that the genetic events leading to these 2 human cancers may proceed along different pathways.