Barks J H, Thompson F H, Taetle R, Yang J M, Stone J F, Wymer J A, Khavari R, Guan X Y, Trent J M, Pinkel D, Nelson M A
Graduate Interdisciplinary Program in Genetics, University of Arizona, Tucson, USA.
Genes Chromosomes Cancer. 1997 Aug;19(4):278-85.
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 B 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.
DNA扩增是肿瘤进展的一个重要机制，它使癌细胞能够上调关键基因的表达，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）的研究显示，在7个黑色素瘤细胞系和B存档转移性黑色素瘤病变中，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，并解决核型和CGH结果之间的差异，我们使用针对20号染色体的全染色体涂染剂，对13个黑色素瘤细胞系（包括用于CGH的7个细胞系）和9个原发性黑色素瘤标本的中期细胞进行了荧光原位杂交（FISH）分析。所有13个细胞系（100%）和8/9个原发性肿瘤（89%）相对于肿瘤倍性均显示有额外的20号染色体拷贝。此外，6/14个细胞系（43%）和2/8个原发性肿瘤（25%）显示有标准细胞遗传学以前未检测到的20号染色体易位物质。在一个细胞系中也发现了基因扩增的细胞学证据，该细胞系含有一个add(20)(p13)，额外的DNA来自20q序列。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位于20号染色体的长臂上。
