Increased chromosome 20 copy number detected by fluorescence in situ hybridization (FISH) in malignant melanoma

Increased chromosome 20 copy number detected by fluorescence in situ hybridization (FISH) in malignant melanoma
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DOI:
10.1002/(sici)1098-2264(199708)19:4
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发表时间:
1997-08-01
影响因子:
3.7
通讯作者:
Nelson, MA
Nelson, MA
中科院分区:
医学2区
文献类型:
--
作者:
Barks, JH;Thompson, FH;Nelson, MA

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DNA扩增是肿瘤进展的重要机制,它允许癌细胞上调关键基因的表达,例如癌基因和赋予耐药性的基因。最近使用比较基因组杂交 (CGH) 的研究揭示了 7 个黑色素瘤细胞系和 8 个档案转移性黑色素瘤病灶中 20q 序列的 DNA 拷贝数增加。为了更详细地评估 20 号染色体异常并解决核型与 CGH 结果之间的差异,我们使用 20 号染色体特异的全染色体染色对 13 个黑色素瘤细胞系(包括用于 CGH 的 7 个系)和 9 个原发性黑色素瘤样本中的中期细胞进行 FISH 分析。所有 13 个细胞系 (100%) 和 8/9 原发性肿瘤 (89%) 均显示相对于肿瘤倍性的 20 号染色体额外拷贝。此外,6/14 细胞系 (43%) 和 2/8 原发性肿瘤 (25%) 显示出先前标准细胞遗传学未检测到的易位 20 号染色体物质。在一种细胞系中也发现了基因扩增的细胞学证据,该细胞系含有 add(20)(p13),另外还有来自 20q 序列的 DNA。这些数据表明,对黑色素瘤发病机制重要的一个或多个基因的过度表达存在于 20 号染色体的长臂上。 (C) 1997 Wiley-Liss, Inc.
DNA amplification is an important mechanism of tumor progression that allows cancer cells to up-regulate the expression of critical genes such as oncogenes and genes conferring drug resistance. Recent studies using comparative genomic hybridization (CGH) revealed increased DNA copies of 20q sequences in 7 melanoma cell lines and 8 archival metastatic melanoma lesions. To evaluate chromosome 20 abnormalities in more detail and to resolve discrepancies between karyotype and CGH findings, we performed FISH analysis of metaphase cells in 13 melanoma cell lines (including the 7 lines used for CGH) and 9 primary melanoma specimens by using a whole chromosome paint specific for chromosome 20. All 13 cell lines (100%) and 8/9 primary tumors (89%) showed extra copies of chromosome 20 relative to tumor ploidy. Additionally, 6/14 cell lines (43%) and 2/8 primary tumors (25%) showed translocated chromosome 20 material previously undetected by standard cytogenetics. Cytologic evidence for gene amplification was also found in one cell line, which contained an add(20)(p13), with additional DNA being derived from 20q sequences. These data suggest that overrepresentation of a gene or genes important for melanoma pathogenesis resides on the long arm of chromosome 20. (C) 1997 Wiley-Liss, Inc.