Analysis of ovarian cancer cell lines using array-based comparative genomic hybridization
Analysis of ovarian cancer cell lines using array-based comparative genomic hybridization
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DOI：
10.1002/path.1681
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发表时间：
2005-01-01
影响因子：
7.3
通讯作者：
Tomlinson, IPM
中科院分区：
文献类型：
--
作者：
Lambros, MBK;Fiegler, H;Tomlinson, IPM
在这项研究中，23卵巢癌细胞系进行了筛选，使用阵列比较基因组杂交（aCGH）的基础上大插入克隆在约1 Mb的密度从整个基因组。在染色体臂水平上最常见的复发性变化是4号或4 q的丢失，18 q的丢失和20或20 q的增加;其他复发性变化包括6 q，8 p，9 p，11 p，15 q，16 q，17 p和22 q的丢失和7 q的增加。4 q和18 q的损失一起发生的频率比预期的要高。发现了两种类型的卵巢癌的证据，一种是典型的近三倍体，其特征是染色体变化的频率通常较高（特别是4p，4 q，13 q，15 q，16 p，16 q，18 p和18 q的丢失），另一种是典型的近二倍体/四倍体，总体变化较少，但9 p丢失，9 q增加和20 p增加的频率相对较高。还检测到多种新的变化（扩增、纯合缺失、获得或丢失的离散区域、变化的小重叠区域和频繁变化的克隆），每种变化都可能指示癌基因或肿瘤抑制基因座的位置。例如，在染色体11 q13上发现至少两个扩增区域，一个包括cyclin D1，另一个包括候选癌基因PAK 1，在11 q22上靠近孕酮受体基因和一簇基质金属蛋白酶位点也检测到扩增。其他潜在的致癌基因，映射到本研究发现的区域，包括细胞周期蛋白E和PIK 3C 2G。缺失区域的候选肿瘤抑制基因包括CDKN 2C、SMAD 4相互作用蛋白和RASSF 2。版权所有（C）2004大不列颠和爱尔兰病理学会。出版社：John Wiley Sons，Ltd
In this study, 23 ovarian cancer cell lines were screened using array-comparative genomic hybridization (aCGH) based on large-insert clones at about 1 Mb density from throughout the genome. The most frequent recurrent changes at the level of the chromosome arm were loss of chromosome 4 or 4q, loss of 18q and gain of 20 or 20q; other recurrent changes included losses of 6q, 8p, 9p, 11p, 15q, 16q, 17p, and 22q, and gain of 7q. Losses of 4q and 18q occurred together more often than expected. Evidence was found for two types of ovarian cancer, one typically near-triploid and characterized by a generally higher frequency of chromosomal changes (especially losses of 4p, 4q, 13q, 15q, 16p, 16q, 18p and 18q), and the other typically near-diploid/tetraploid and with fewer changes overall, but with relatively high frequencies of 9p loss, 9q gain, and 20p gain. Multiple novel changes (amplifications, homozygous deletions, discrete regions of gain or loss, small overlapping regions of change and frequently changed clones) were also detected, each of which might indicate the locations of oncogenes or tumour suppressor loci. For example, at least two regions of amplification on chromosome 11q13, one including cyclin D1 and the other the candidate oncogene PAK1, were found. Amplification on 11q22 near the progesterone receptor gene and a cluster of matrix metalloproteinase loci was also detected. Other potential oncogenes, which mapped to regions found by this study, included cyclin E and PIK3C2G. Candidate tumour suppressor genes in regions of loss included CDKN2C, SMAD4-interacting protein and RASSF2. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.