Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer.
Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer.
复制标题
DOI：
10.1158/1078-0432.ccr-08-2036
复制
发表时间：
2009-03-15
期刊：
影响因子：
--
通讯作者：
Scher HI
中科院分区：
文献类型：
--
作者：
Leversha MA;Han J;Asgari Z;Danila DC;Lin O;Gonzalez-Espinoza R;Anand A;Lilja H;Heller G;Fleisher M;Scher HI
目的 评估通过使用 CellSearch 系统分离的进行性去势抵抗性转移性前列腺癌 (CRPC) 患者的循环肿瘤细胞 (CTC) 的荧光原位杂交来表征基因拷贝数变化的可行性。我们使用包含雄激素受体 (AR) 和 MYC 基因的探针组合对从 77 名患有转移性 CRPC 的男性收集的 CTC 样本进行 FISH 分析。在 37.5% 的分析样本中检测到 AR 高水平染色体扩增，55.8% 的 MYC 相对扩增。在 CTC 计数低于 10 的样本中未检测到此类异常，反映出这些较低计数样本的确定困难。从我们的患者队列中分离出的 CTC 呈现出与晚期肿瘤报告的非常相似的分子细胞遗传学特征，因此证明 CTC 分析可以成为常规肿瘤分析的有价值的非侵入性替代物。此外，我们证明这些患者中有多达 50% 的 AR 基因座显着扩增，表明雄激素信号传导在晚期前列腺癌中继续发挥重要作用。
To assess the feasibility of characterizing gene copy number alteration by fluorescence in situ hybridization of circulating tumor cells (CTC) isolated using the CellSearch system in patients with progressive castration resistant metastatic prostate cancer (CRPC). We used probe combinations that included the androgen receptor (AR) and MYC genes for FISH analysis of CTC samples collected from 77 men with metastatic CRPC. High-level chromosomal amplification of AR was detected in 37.5% of samples analyzed, and relative gain of MYC in 55.8%. No such abnormalities were detected in samples with CTC counts of less than 10, reflecting ascertainment difficulty in these lower count samples. The CTC isolated from our patient cohort present a very similar molecular cytogenetic profile to that reported for late-stage tumors, and thus demonstrate that analysis of CTC can be a valuable, noninvasive surrogate for routine tumor profiling. Furthermore, we demonstrate that as many as 50% of these patients have substantial amplification of the AR locus, indicating that androgen signaling continues to play an important role in late-stage prostate cancer.