Genomic alterations indicate tumor origin and varied metastatic potential of disseminated cells from prostate cancer patients.
Genomic alterations indicate tumor origin and varied metastatic potential of disseminated cells from prostate cancer patients.
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DOI：
10.1158/0008-5472.can-08-0812
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发表时间：
2008-07-15
期刊：
影响因子：
11.2
通讯作者：
Vessella, Robert L.
中科院分区：
文献类型：
--
作者：
Holcomb, Ilona N.;Grove, Douglas I.;Kinnunen, Martin;Friedman, Cynthia L.;Gallaher, Ian S.;Morgan, Todd M.;Sather, Cassandra L.;Delrow, Jeffrey J.;Nelson, Peter S.;Lange, Paul H.;Ellis, William J.;True, Lawrence D.;Young, Janet M.;Hsu, Li;Trask, Barbara J.;Vessella, Robert L.
与进展为转移性疾病的患者相比，可以从更大比例的前列腺癌患者的骨髓中分离出播散性上皮细胞。为了更好地了解这些细胞，我们描述了它们的基因组改变。我们首先提出了一种阵列比较基因组杂交方法，能够检测通常可以从前列腺癌患者的骨髓穿刺液中获得的少量播散细胞中的基因组变化。我们在11名转移性患者的散布细胞库中显示了多个拷贝数变化区域，包括前列腺癌中常见的改变，例如8 p丢失、8 q增加以及Xq上雄激素受体基因的增加。我们在来自器官局限性疾病患者的48个播散细胞池中发现了越来越少的显著基因组改变。然而，我们确定了这些样本与文献中报道的相应原发性肿瘤和前列腺癌改变所共有的变化，证明这些细胞与晚期疾病中的细胞一样，是播散性肿瘤细胞（DTC）。我们还表明，从先进的和局部疾病的患者DTC共享几个异常，包括损失含有细胞粘附基因和改变报告与疾病进展。这些共同的改变可能赋予传播或建立继发性疾病的能力。总体而言，基因组偏差谱是晚期疾病DTC转移能力以及局部疾病DTC转移能力差异的证据。我们的分析奠定了基础，阐明DTC基因组变异和进行性前列腺癌之间的关系。
Disseminated epithelial cells can be isolated from the bone marrow of a far greater fraction of prostate-cancer patients than the fraction of patients who progress to metastatic disease. To provide a better understanding of these cells, we have characterized their genomic alterations. We first present an array comparative genomic hybridization method capable of detecting genomic changes in the small number of disseminated cells that can typically be obtained from bone-marrow aspirates of prostate-cancer patients. We show multiple regions of copy-number change, including alterations common in prostate cancer, such as 8p loss, 8q gain, and gain encompassing the androgen-receptor gene on Xq, in the disseminated cell pools from 11 metastatic patients. We found fewer and less striking genomic alterations in the 48 pools of disseminated cells from patients with organ-confined disease. However, we identify changes shared by these samples with their corresponding primary tumors and prostate-cancer alterations reported in the literature, evidence that these cells, like those in advanced disease, are disseminated tumor cells (DTCs). We also demonstrate that DTCs from patients with advanced and localized disease share several abnormalities, including losses containing cell-adhesion genes and alterations reported to associate with progressive disease. These shared alterations might confer the capability to disseminate or establish secondary disease. Overall, the spectrum of genomic deviations is evidence for metastatic capacity in advanced-disease DTCs and variation in that capacity in DTCs from localized disease. Our analysis lays the foundation for elucidation of the relationship between DTC genomic alterations and progressive prostate cancer.