Clonal architectures predict clinical outcome in clear cell renal cell carcinoma
Clonal architectures predict clinical outcome in clear cell renal cell carcinoma
复制标题
克隆结构预测透明细胞肾细胞癌的临床结果
DOI：
10.1038/s41467-019-09241-7
复制
发表时间：
2019-03-18
影响因子：
16.6
通讯作者：
Zhang, Baifeng
中科院分区：
文献类型：
--
作者：
Huang, Yi;Wang, Jiayin;Zhang, Baifeng
肾透明细胞癌（ccRCC）的遗传景观已被广泛研究，但其演变模式仍不清楚。在这里，我们分析了来自三个不同人群的473例患者的克隆结构。我们发现，不同种群和进化阶段的突变特征差异很大。ccRCC的进化模式具有很大的患者间异质性，del（3p）被认为是常见的最早事件，随后是三个早期起点：VHLandPBRM 1突变，del（14 q）和其他体细胞拷贝数改变（SCNA），包括amp（7），del（1p）和del（6q）。我们确定了具有不同克隆结构和免疫浸润的ccRCC的三种预后亚型：富含VHL但缺乏BAP1突变的长寿患者具有高水平的Th17和CD8+T细胞，而具有高SCNA负荷的短命患者具有高水平的Th17和Th2细胞，突出了评估ccRCC临床管理中演变模式的重要性。
The genetic landscape of clear cell renal cell carcinoma (ccRCC) had been investigated extensively but its evolution patterns remained unclear. Here we analyze the clonal architectures of 473 patients from three different populations. We find that the mutational signatures vary substantially across different populations and evolution stages. The evolution patterns of ccRCC have great inter-patient heterogeneities, with del(3p) being regarded as the common earliest event followed by three early departure points:VHLandPBRM1mutations, del(14q) and other somatic copy number alterations (SCNAs) including amp(7), del(1p) and del(6q). We identify three prognostic subtypes of ccRCC with distinct clonal architectures and immune infiltrates: long-lived patients, enriched withVHLbut depleted ofBAP1mutations, have high levels of Th17 and CD8+T cells while short-lived patients with high burden of SCNAs have high levels of Tregs and Th2 cells, highlighting the importance of evaluating evolution patterns in the clinical management of ccRCC.