Forozan F, Mahlamäki E H, Monni O, Chen Y, Veldman R, Jiang Y, Gooden G C, Ethier S P, Kallioniemi A, Kallioniemi O P
Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892-4470, USA.
Cancer Res. 2000 Aug 15;60(16):4519-25.
Breast cancer cell lines provide a useful starting point for the discovery and functional analysis of genes involved in breast cancer. Here, we studied 38 established breast cancer cell lines by comparative genomic hybridization (CGH) to determine recurrent genetic alterations and the extent to which these cell lines resemble uncultured tumors. The following chromosomal gains were observed: 8q (75%), 1q (61%), 20q (55%), 7p (44%), 3q (39%), 5p (39%), 7q (39%), 17q (33%), 1p (30%), and 20p (30%), and the most common losses were: 8p (58%), 18q (58%), 1p (42%), Xp (42%), Xq (42%), 4p (36%), 11q (36%), 18p (33%), 10q (30%), and 19p (28%). Furthermore, 35 recurrent high-level amplification sites were identified, most often involving 8q23 (37%), 20q13 (29%), 3q25-q26 (24%), 17q22-q23 (16%), 17q23-q24 (16%), 1p13 (11%), 1q32 (11%), 5p13 (11%), 5p14 (11%), 11q13 (11%), 17q12-q21 (11%), and 7q21-q22 (11%). A comparison of DNA copy number changes found in the cell lines with those reported in 17 published studies (698 tumors) of uncultured tumors revealed a substantial degree of overlap. CGH copy number profiles may facilitate identification of important new genes located at the hotspots of such chromosomal alterations. This was illustrated by analyzing expression levels of 1236 genes using cDNA microarrays in four of the cell lines. Several highly overexpressed genes (such as RCH1 at 17q23, TOPO II at 17q21-q22, as well as CAS and MYBL2 at 20q13) were involved in these recurrent DNA amplifications. In conclusion, DNA copy number profiles were generated by CGH for most of the publicly available breast cancer cell lines and were made available on a web site (http://www.nhgri.nih.gov/DIR/CGB/++ +CR2000). This should facilitate the correlative analysis of gene expression and copy number as illustrated here by the finding by cDNA microarrays of several overexpressed genes that were amplified.
乳腺癌细胞系为乳腺癌相关基因的发现和功能分析提供了一个有用的起点。在此，我们通过比较基因组杂交（CGH）研究了38个已建立的乳腺癌细胞系，以确定复发性基因改变以及这些细胞系与未培养肿瘤的相似程度。观察到以下染色体增加：8q（75%）、1q（61%）、20q（55%）、7p（44%）、3q（39%）、5p（39%）、7q（39%）、17q（33%）、1p（30%）和20p（30%），最常见的缺失为：8p（58%）、18q（58%）、1p（42%）、Xp（42%）、Xq（42%）、4p（36%）、11q（36%）、18p（33%）、10q（30%）和19p（28%）。此外，还鉴定出35个复发性高水平扩增位点，最常见的涉及8q23（37%）、20q13（29%）、3q25 - q26（24%）、17q22 - q23（16%）、17q23 - q24（16%）、1p13（11%）、1q32（11%）、5p13（11%）、5p14（11%）、11q13（11%）、17q12 - q21（11%）和7q21 - q22（11%）。将细胞系中发现的DNA拷贝数变化与17项已发表的未培养肿瘤研究（698个肿瘤）中报告的变化进行比较，发现有相当程度的重叠。CGH拷贝数谱可能有助于识别位于此类染色体改变热点区域的重要新基因。通过使用cDNA微阵列分析四个细胞系中1236个基因的表达水平对此进行了说明。一些高度过表达的基因（如17q23处的RCH1、17q21 - q22处的TOPO II以及20q13处的CAS和MYBL2）参与了这些复发性DNA扩增。总之，通过CGH为大多数公开可用的乳腺癌细胞系生成了DNA拷贝数谱，并在网站（http://www.nhgri.nih.gov/DIR/CGB/++ +CR2000）上提供。这应该有助于基因表达和拷贝数相关性分析，如此处通过cDNA微阵列发现几个扩增的过表达基因所说明的那样。
