The Evolutionary Landscape of Localized Prostate Cancers Drives Clinical Aggression
The Evolutionary Landscape of Localized Prostate Cancers Drives Clinical Aggression
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DOI：
10.1016/j.cell.2018.03.029
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发表时间：
2018-05-03
期刊：
影响因子：
64.5
通讯作者：
Boutros, Paul C.
中科院分区：
文献类型：
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作者：
Espiritu, Shadrielle Melijah G.;Liu, Lydia Y.;Boutros, Paul C.
大多数新诊断的前列腺癌生长缓慢，具有很长的自然生活史。然而，一个子集可以转移致命的后果。我们重建了293例与临床结果数据相关的局限性前列腺肿瘤的复发。59%的患者中检测到多个亚克隆，并且特定的亚克隆结构与不良临床病理特征相关。早期肿瘤发展的特征在于点突变和缺失，随后是亚克隆扩增和三核苷酸突变特征的变化。在亚克隆多样化之前或之后选择性地突变特定基因，包括MTOR、NKX 3 -1和RB 1。低风险单克隆肿瘤患者在初次治疗后很少复发（7%），而高风险多克隆肿瘤患者经常复发（61%）。对于局限性前列腺癌的复发，索引活检中存在多个亚克隆可能是必要的，但不是充分的，这表明在适合主动监测的低风险肿瘤的前瞻性研究中应研究进化感知的生物标志物。
The majority of newly diagnosed prostate cancers are slow growing, with a long natural life history. Yet a subset can metastasize with lethal consequences. We reconstructed the phylogenies of 293 localized prostate tumors linked to clinical outcome data. Multiple subclones were detected in 59% of patients, and specific subclonal architectures associate with adverse clinicopathological features. Early tumor development is characterized by point mutations and deletions followed by later subclonal amplifications and changes in trinucleotide mutational signatures. Specific genes are selectively mutated prior to or following subclonal diversification, including MTOR, NKX3-1, and RB1. Patients with low-risk monoclonal tumors rarely relapse after primary therapy (7%), while those with high-risk polyclonal tumors frequently do (61%). The presence of multiple subclones in an index biopsy may be necessary, but not sufficient, for relapse of localized prostate cancer, suggesting that evolution-aware biomarkers should be studied in prospective studies of low-risk tumors suitable for active surveillance.