Genomic profiling of isolated circulating tumor cells from metastatic breast cancer patients.
Genomic profiling of isolated circulating tumor cells from metastatic breast cancer patients.
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DOI：
10.1158/0008-5472.can-11-3017
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发表时间：
2013-01-01
期刊：
影响因子：
11.2
通讯作者：
Park JW
中科院分区：
文献类型：
--
作者：
Magbanua MJ;Sosa EV;Roy R;Eisenbud LE;Scott JH;Olshen A;Pinkel D;Rugo HS;Park JW
血液循环肿瘤细胞（CTCs）的分子表征在技术上具有挑战性，因为细胞罕见且难以分离。我们开发了一种新的方法，通过免疫磁富集和荧光活化细胞分选（IE/FACS）从血液中分离ctc。通过阵列比较基因组杂交（aCGH）对分离的ctc进行全基因组拷贝数分析。在临床研究中，从181例转移性乳腺癌患者中分离出ctc，其中102例成功分析，包括来自5例患者的匹配档案原发肿瘤。ctc显示了广泛的拷贝数改变，包括先前报道的乳腺癌。与两个已发表的原发性乳腺肿瘤aCGH数据集比较，发现复发性基因组拷贝数畸变的频率相似。此外，ctc的系列测试证实了可重复性，并表明随着时间的推移基因组发生了变化。ctc与匹配的档案原发肿瘤的比较证实了具有显著差异的共同谱系。我们证明了通过IE/FACS从造血细胞中分离高纯度ctc并通过aCGH分析对其进行分析是可行的。我们的方法可用于探索与癌症进展有关的基因组事件，并以相对非侵入性的方式监测临床试验中靶向治疗的治疗效果。
Molecular characterization of circulating tumor cells (CTCs) from blood is technically challenging because cells are rare and difficult to isolate. We developed a novel approach to isolate CTCs from blood via immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS). Isolated CTCs were subjected to genome-wide copy number analysis via array comparative genomic hybridization (aCGH). In clinical studies, CTCs were isolated from 181 patients with metastatic breast cancer, 102 of which were successfully profiled, including matched archival primary tumor from five patients. CTCs revealed a wide range of copy number alterations including those previously reported in breast cancer. Comparison with two published aCGH datasets of primary breast tumors revealed similar frequencies of recurrent genomic copy number aberrations. In addition, serial testing of CTCs confirmed reproducibility and indicated genomic change over time. Comparison of CTCs with matched archival primary tumors confirmed shared lineage with notable divergence. We demonstrate that it is feasible to isolate CTCs away from hematopoietic cells with high purity via IE/FACS and profile them via aCGH analysis. Our approach may be utilized to explore genomic events involved in cancer progression and to monitor therapeutic efficacy of targeted therapies in clinical trials in a relatively non-invasive manner.