The complicated copy number alterations in chromosome 7 of a lung cancer cell line is explained by a model based on repeated breakage-fusion-bridge cycles
The complicated copy number alterations in chromosome 7 of a lung cancer cell line is explained by a model based on repeated breakage-fusion-bridge cycles
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DOI：
10.1016/j.cancergencyto.2008.04.005
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发表时间：
2008-08-01
影响因子：
--
通讯作者：
Yamasaki, Tomoaki
中科院分区：
文献类型：
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作者：
Kitada, Kunio;Yamasaki, Tomoaki
之前通过接触抗癌药物紫杉醇建立的耐药肺癌细胞系 PTX250 的 MDR1/ABCB1 基因座区域的拷贝数有所增加。此外，侧翼区域也表现出异常的拷贝数，使得7号染色体的拷贝数谱变得复杂。在这项研究中，我们测试了断裂-融合-桥（BFB）循环模型是否可以解释这种拷贝数变化。使用荧光原位杂交 (FISH) 和涂色探针进行的分析表明，异常染色体（称为 7 号染色体 (amp)）源自完整的 7 号染色体。使用高密度比较基因组杂交阵列，我们详细检查了拷贝数谱，并将 7 号染色体 (amp) 分为七个片段。根据使用间期和中期 FISH 分析确定的每个片段的拷贝数，我们构建了复杂拷贝数改变的形成模型。该模型预设了六次 BFB 循环和通过修复断端来终止循环。在 7(amp) 染色体中观察到的片段的位置和方向与模型预测的非常吻合。端粒的添加也得到了细胞遗传学的证实。总之，可以得出结论，在 7 号染色体 (amp) 中发现的复杂拷贝数改变是通过重复的 BFB 循环从完整的 7 号染色体产生的。 (C) 2008 Elsevier Inc. 保留所有权利。
The drug-resistant lung cancer cell line PTX250, which has been previously established by exposure to an anti-cancer drug paclitaxel, has an increased copy number in the MDR1/ABCB1 locus region. In addition, the flanking regions also exhibit aberrant copy numbers, making the copy number profile of chromosome 7 complicated. In this study, we tested whether the breakage-fusion-bridge (BFB) cycle model can explain such copy number alterations. An analysis using fluorescence in situ hybridization (FISH) with a painting probe demonstrated that the aberrant chromosome, designated chromosome 7(amp), was derived from an intact chromosome 7. Using high-density comparative genomic hybridization arrays, we examined the copy number profile in detail and divided chromosome 7(amp) into seven segments. Based on copy numbers of each segment, which were determined using interphase- and metaphase-FISH analysis, we constructed a formation model for the complicated copy number alteration. Six-time BFB cycles and the cycle-termination by healing of broken ends were presupposed in the model. Locations and orientations of the segments observed in chromosome 7(amp) agreed well with those predicted from the model. Telomere addition was also cytogenetically confirmed. In all, it could be concluded that the complicated copy number alteration found in chromosome 7(amp) is generated from the intact chromosome 7 by the repeated BFB cycles. (C) 2008 Elsevier Inc. All rights reserved.