Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK; Renal and Skin Units, the Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK.
Translational Cancer Therapeutics Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Cell. 2018 Apr 19;173(3):581-594.e12. doi: 10.1016/j.cell.2018.03.057. Epub 2018 Apr 12.
Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct patterns of metastatic dissemination were observed, including rapid progression to multiple tissue sites seeded by primary tumors of monoclonal structure. By contrast, we observed attenuated progression in cases characterized by high primary tumor heterogeneity, with metastatic competence acquired gradually and initial progression to solitary metastasis. Finally, we observed early divergence of primitive ancestral clones and protracted latency of up to two decades as a feature of pancreatic metastases.
透明细胞肾细胞癌 (ccRCC) 表现出广泛的转移表型，但迄今为止尚未对此进行系统研究。在这里，我们分析了 100 名转移性 ccRCC 患者的 575 份原发和 335 份转移活检，包括两例死后取样。染色体复杂性赋予了转移性能力，我们发现 9p 缺失是驱动转移和 ccRCC 相关死亡率的高度选择事件（p=0.0014）。观察到不同的转移传播模式，包括由单克隆结构的原发肿瘤快速播散到多个组织部位。相比之下，我们观察到具有高原发肿瘤异质性的病例进展减弱，转移性能力逐渐获得，最初进展为单发转移。最后，我们观察到原始祖细胞克隆的早期分歧和长达二十年的潜伏期，这是胰腺转移的一个特征。
