Detection of circulating tumour cell clusters in human glioblastoma.

Detection of circulating tumour cell clusters in human glioblastoma.
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DOI:
10.1038/s41416-018-0186-7
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发表时间:
2018-08
影响因子:
8.8
通讯作者:
Aceto N
Aceto N
中科院分区:
医学1区
文献类型:
--
作者:
Krol I;Castro-Giner F;Maurer M;Gkountela S;Szczerba BM;Scherrer R;Coleman N;Carreira S;Bachmann F;Anderson S;Engelhardt M;Lane H;Evans TRJ;Plummer R;Kristeleit R;Lopez J;Aceto N

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人胶质母细胞瘤(GBM)是一种高度侵袭性、侵袭性和血管丰富的恶性脑癌。个别循环肿瘤细胞(CTC)在GBM患者中零星发现,但尚不清楚这种疾病中是否会产生多细胞CTC簇,以及它们是否可以绕过血脑屏障的物理障碍。 在此,我们在一项使用微管抑制剂BAL 101553的开放标签I/IIa期研究中,评估了13例进展性GBM患者在多个时间点的CTC存在和组成。我们观察到CTC集群范围从2到23个细胞,并在多个采样时间点在GBM患者与多形性和广泛的坏死,在整个疾病进展。GBM CTC簇的外显子组测序突出了58个癌症相关基因中的变体,包括ATM,PMS 2,POLE,APC,XPO 1,TFRC,JAK 2,ERBB 4和ALK。总之,我们的研究结果代表了GBM中存在CTC簇的第一个证据。
Human glioblastoma (GBM) is a highly aggressive, invasive and hypervascularised malignant brain cancer. Individual circulating tumour cells (CTCs) are sporadically found in GBM patients, yet it is unclear whether multicellular CTC clusters are generated in this disease and whether they can bypass the physical hurdle of the blood–brain barrier.  Here, we assessed CTC presence and composition at multiple time points in 13 patients with progressing GBM during an open-label phase 1/2a study with the microtubule inhibitor BAL101553. We observe CTC clusters ranging from 2 to 23 cells and present at multiple sampling time points in a GBM patient with pleomorphism and extensive necrosis, throughout disease progression. Exome sequencing of GBM CTC clusters highlights variants in 58 cancer-associated genes including ATM, PMS2, POLE, APC, XPO1, TFRC, JAK2, ERBB4 and ALK. Together, our findings represent the first evidence of the presence of CTC clusters in GBM.
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