Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma
Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma
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DOI：
10.1038/sj.eye.6701906
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发表时间：
2006-04-01
期刊：
影响因子：
3.9
通讯作者：
Sisley, K
中科院分区：
文献类型：
--
作者：
Cross, NA;Ganesh, A;Sisley, K
目的3号染色体丢失是葡萄膜黑色素瘤的常见事件，与肝转移和预后不良有关。3号染色体的整个拷贝通常丢失（3号单体）;然而，一小部分肿瘤表现出3号染色体的部分缺失。对这些肿瘤的分析可以鉴定肿瘤抑制基因（TSG），这些基因是单体3的分子靶点。因此，本研究的目的是确定这些部分缺失的3号染色体在葡萄膜melanomas.Methods的位置进行微卫星分析和限制性片段长度多态性分析52原发性葡萄膜黑色素瘤使用19个标记位于两臂的3号染色体。进行细胞遗传学分析和荧光原位杂交，在可能的情况下，以确认分子findings.Results研究的52个肿瘤，5个肿瘤（10%）表现出洛在一个或多个信息标记，但保留杂合性观察在3号染色体上的其他位点，与3号染色体的结构异常的存在相一致。与以前的发现一致，这些肿瘤中的洛缺失模式表明在3 p25 -26和3q附近存在缺失，在3 p11-结论这些结果表明3号染色体上存在几个肿瘤抑制基因座，并支持葡萄膜黑色素瘤中3号单体的高比率是由几个TSG的破坏驱动的观点位于3号染色体的两臂上。
Purpose Loss of chromosome 3 is a frequent event in uveal melanomas, which is associated with hepatic metastases and a poor prognosis. The entire copy of chromosome 3 is usually lost (monosomy 3); however, a small subset of tumours demonstrate partial deletions of chromosome 3. Analysis of these tumours may allow the identification of tumour suppressor genes (TSGs) that are the molecular target of monosomy 3. Therefore, the purpose of this investigation was to determine the location of these partial deletions of chromosome 3 in uveal melanomas.Methods Microsatellite analysis and restriction fragment-length polymorphism analysis were performed on 52 primary uveal melanomas using 19 markers located on both arms of chromosome 3. Cytogenetic analysis and fluorescence in situ hybridisation were performed, where possible, to confirm molecular findings.Results Of 52 tumours studied, five tumours (10%) demonstrated LOH at one or more informative markers, but retention of heterozygosity was observed at other loci on chromosome 3, consistent with the presence of structural abnormalities to chromosome 3. Consistent with previous findings, the pattern of LOH in these tumours indicates the presence of deletions around 3p25-26 and on 3q, and that a new target region at 3p11-14 is preferentially deleted.Conclusions These results indicate the presence of several tumour suppressor loci on chromosome 3 and support the notion that the high rate of monosomy 3 in uveal melanoma is driven by disruption of several TSGs located on both arms of chromosome 3.