Utility of Single-Cell Genomics in Diagnostic Evaluation of Prostate Cancer
Utility of Single-Cell Genomics in Diagnostic Evaluation of Prostate Cancer
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DOI：
10.1158/0008-5472.can-17-1138
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发表时间：
2018-01-15
期刊：
影响因子：
11.2
通讯作者：
Krasnitz, Alexander
中科院分区：
文献类型：
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作者：
Alexander, Joan;Kendall, Jude;Krasnitz, Alexander
区分惰性和侵袭性疾病是前列腺癌诊断的主要挑战。由于遗传异质性和复杂性可能会影响临床结果，我们已经开始了单肿瘤细胞基因组学的研究。在这项研究中，我们证明了前列腺核心活检单细胞核的稀疏DNA测序是评估肿瘤生长和侵袭性的定量参数的丰富来源。这些包括克隆群体的存在，这些群体的系统发育结构，在这些群体中的拷贝数变化的复杂程度，并与克隆拷贝数签名的细胞的比例的措施。这些参数都显示出与前列腺恶性程度的测量良好的相关性，Gleason评分，来自个体前列腺活检组织芯。值得注意的是，一个更准确的恶性肿瘤的组织病理学测量，手术格里森评分，同意更好地与这些诊断活检的基因组参数比诊断格里森评分和诊断组织病理学的相关措施。这是高度相关的，因为主要治疗决定取决于活检而不是手术标本。因此，单细胞分析有可能增强传统的核心组织病理学，提高风险评估的客观性和准确性，并为治疗决策提供信息。(C)2017年AACR。
A distinction between indolent and aggressive disease is a major challenge in diagnostics of prostate cancer. As genetic heterogeneity and complexity may influence clinical outcome, we have initiated studies on single tumor cell genomics. In this study, we demonstrate that sparse DNA sequencing of single-cell nuclei from prostate core biopsies is a rich source of quantitative parameters for evaluating neoplastic growth and aggressiveness. These include the presence of clonal populations, the phylogenetic structure of those populations, the degree of the complexity of copy-number changes in those populations, and measures of the proportion of cells with clonal copy-number signatures. The parameters all showed good correlation to the measure of prostatic malignancy, the Gleason score, derived from individual prostate biopsy tissue cores. Remarkably, a more accurate histopathologic measure of malignancy, the surgical Gleason score, agrees better with these genomic parameters of diagnostic biopsy than it does with the diagnostic Gleason score and related measures of diagnostic histopathology. This is highly relevant because primary treatment decisions are dependent upon the biopsy and not the surgical specimen. Thus, single-cell analysis has the potential to augment traditional core histopathology, improving both the objectivity and accuracy of risk assessment and inform treatment decisions. (C) 2017 AACR.