Localization of multiple melanoma tumor-suppressor genes on chromosome 11 by use of homozygosity mapping-of-deletions analysis
Localization of multiple melanoma tumor-suppressor genes on chromosome 11 by use of homozygosity mapping-of-deletions analysis
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DOI：
10.1086/302999
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发表时间：
2000-08-01
影响因子：
9.8
通讯作者：
Fountain, JW
中科院分区：
文献类型：
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作者：
Goldberg, EK;Glendening, JM;Fountain, JW
杂合性缺失（LOH）研究表明，一个或多个11号染色体肿瘤抑制基因与皮肤黑色素瘤以及各种其他形式的人类癌症的发展有关。在本研究中，我们通过使用缺失纯合定位（homozysity mapping of deletion, homd）分析鉴定了该染色体上的多个独立关键区域。这种分析方法包括使用高度多态性微卫星标记和统计学来识别不匹配的黑色素瘤细胞系dna中的半合子缺失区域。缺失区域的定义是在大于或等于5个相邻标记处存在一个扩展的纯合子区域（ERH），其统计概率小于或等于0.001。尽管在细胞系中观察到更高的丢失频率（40例中有24例[60%]对47例中有16例[34%]），但在未培养的黑色素瘤中发现的显著erh在性质上与LOH分析中发现的缺失相似。总体而言，在11号染色体上鉴定出6个重叠缺失小区域，分别位于D11S1338/D11S907 （11p13-15.5 [SRO1]）、D11S1344/D11S11385 （11p11.2 [SRO2]）、D11S917/D11S1886 （11q21-22.3 [SRO3]）、D11S927/D11S4094 （11q23 [SRO4]）、AFM210ve3/D11S990 （11q24 [SR05]）和D11S1351/D11S4123 （11q24-25 [SRO6]）。我们建议，在肿瘤抑制基因定位中，homd分析可以作为LOH分析的辅助手段。
Loss-of-heterozygosity (LOH) studies have implicated one or more chromosome 11 tumor-suppressor gene(s) in the development of cutaneous melanoma as well as a variety of other forms of human cancer. In the present study, we have identified multiple independent critical regions on this chromosome by use of homozygosity mapping of deletions (HOMOD) analysis. This method of analysis involved the use of highly polymorphic microsatellite markers and statistics to identify regions of hemizygous deletion in unmatched melanoma cell line DNAs. Regions of loss were defined by the presence of an extended region of homozygosity (ERH) at greater than or equal to 5 adjacent markers and having a statistical probability of less than or equal to.001. Significant ERHs were similar in nature to deletions identified by LOH analyses performed on uncultured melanomas, although a higher frequency of loss (24 [60%] of 40 vs. 16 [34%] of 47) was observed in the cell lines. Overall, six small regions of overlapping deletions (SROs) were identified on chromosome 11 flanked by the markers D11S1338/D11S907 (11p13-15.5 [SRO1]), D11S1344/D11S11385 (11p11.2 [SRO2]), D11S917/D11S1886 (11q21-22.3 [SRO3]), D11S927/D11S4094 (11q23 [SRO4]),AFM210ve3/D11S990 (11q24 [SR05]), and D11S1351/D11S4123 (11q24-25 [SRO6]). We propose that HOMOD analysis can be used as an adjunct to LOH analysis in the localization of tumor-suppressor genes.