Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Oxford NIHR Biomedical Research Centre, University of Oxford, UK.
Eur Urol Oncol. 2021 Jun;4(3):358-369. doi: 10.1016/j.euo.2021.02.008. Epub 2021 Apr 20.
Studies characterising genomic changes in prostate cancer (PCa) during natural progression have greatly increased our understanding of the disease. A better understanding of the evolutionary history of PCa would allow advances in diagnostics, prognostication, and novel therapies that together will improve patient outcomes.
To review the molecular heterogeneity of PCa and assess recent efforts to profile intratumoural heterogeneity and clonal evolution.
We screened a total of 1313 abstracts from PubMed published between 2009 and 2020, of which we reviewed 84 full-text articles. We excluded 49, resulting in 35 studies for qualitative analysis.
In studies of primary disease (16 studies, 4793 specimens), there is a lack of consensus regarding the monoclonal or polyclonal origin of primary PCa. There is no consistent mutation giving rise to primary PCa. Detailed clonal analysis of primary PCa has been limited by current techniques. By contrast, clonal relationships between PCa metastases and a potentiating clone have been consistently identified (19 studies, 732 specimens). Metastatic specimens demonstrate consistent truncal genomic aberrations that suggest monoclonal metastatic progenitors.
The relationship between the clonal dynamics of PCa and clinical outcomes needs further investigation. It is likely that this will provide a biological rationale for whether radical treatment of the primary tumour benefits patients with oligometastatic PCa. Future studies on the mutational burden in primary disease at single-cell resolution should permit the identification of clonal patterns underpinning the origin of lethal PCa.
Prostate cancers arise in different parts of the prostate because of DNA mutations that occur by chance at different times. These cancer cells and their origin can be tracked by DNA mapping. In this review we summarise the state of the art and outline what further science is needed to provide the missing answers.
对前列腺癌（PCa）自然进展过程中基因组变化的研究极大地提高了我们对该疾病的认识。更好地了解 PCa 的进化史将有助于推进诊断、预后和新疗法的发展，从而改善患者的预后。
综述 PCa 的分子异质性，并评估最近对肿瘤内异质性和克隆进化进行分析的研究进展。
我们从 2009 年至 2020 年在 PubMed 上总共筛选了 1313 篇摘要，其中我们回顾了 84 篇全文文章。我们排除了 49 篇，对 35 篇进行了定性分析。
在原发性疾病的研究中（16 项研究，4793 个标本），对于原发性 PCa 是单克隆还是多克隆起源，尚无共识。没有一致的突变导致原发性 PCa。由于当前技术的限制，对原发性 PCa 的详细克隆分析受到限制。相比之下，PCa 转移灶与促进克隆之间的克隆关系已得到一致确定（19 项研究，732 个标本）。转移性标本显示出一致的主干基因组异常，提示存在单克隆转移性前体。
PCa 的克隆动力学与临床结局之间的关系需要进一步研究。很可能这将为是否对寡转移性 PCa 患者的原发性肿瘤进行根治性治疗提供生物学依据。未来在单细胞分辨率下对原发性疾病中突变负担的研究应能确定导致致命性 PCa 的克隆模式。
前列腺癌是由于不同时间发生的偶然 DNA 突变而在前列腺的不同部位发生的。这些癌细胞及其起源可以通过 DNA 图谱进行跟踪。在本综述中，我们总结了该领域的最新进展，并概述了进一步的科学研究需要解决的问题。
