Integrative genomic study of Chinese clear cell renal cell carcinoma reveals features associated with thrombus
Integrative genomic study of Chinese clear cell renal cell carcinoma reveals features associated with thrombus
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DOI：
10.1038/s41467-020-14601-9
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发表时间：
2020-02-06
影响因子：
16.6
通讯作者：
Ma, Lu-Lin
中科院分区：
文献类型：
--
作者：
Wang, Xiang-Ming;Lu, Yang;Ma, Lu-Lin
透明细胞肾细胞癌（ccRCC）是一种异质性疾病，其特征因种族而异。中国ccRCC的基因组景观缺乏系统的表征，与肿瘤血栓（ccRCC-TT）相关的ccRCC的特征仍然知之甚少。在这里，我们对110个正常肿瘤对和42个正常肿瘤血栓三联体进行了全外显子组测序，并对来自152名中国ccRCC患者的61个肿瘤-正常对和30个原发性血栓对进行了转录组测序。我们的分析显示，与马兜铃酸（AA）暴露相关的突变特征在中国ccRCC中广泛存在。来自ccRCC-TT患者的肿瘤显示出更高的突变负荷和基因组不稳定性;此外，BAP 1和SETD 2的突变在ccRCC-TT患者中高度富集。此外，有/无TT的患者显示出不同的分子特征。我们报告了中国ccRCC的整合基因组测序，并确定了与癌栓相关的特征，这可能有助于ccRCC的诊断，预后和治疗。
Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with features that vary by ethnicity. A systematic characterization of the genomic landscape of Chinese ccRCC is lacking, and features of ccRCC associated with tumor thrombus (ccRCC-TT) remain poorly understood. Here, we applied whole-exome sequencing on 110 normal-tumor pairs and 42 normal-tumor-thrombus triples, and transcriptome sequencing on 61 tumor-normal pairs and 30 primary-thrombus pairs from 152 Chinese patients with ccRCC. Our analysis reveals that a mutational signature associated with aristolochic acid (AA) exposure is widespread in Chinese ccRCC. Tumors from patients with ccRCC-TT show a higher mutational burden and genomic instability; in addition, mutations in BAP1 and SETD2 are highly enriched in patients with ccRCC-TT. Moreover, patients with/without TT show distinct molecular characteristics. We reported the integrative genomic sequencing of Chinese ccRCC and identified the features associated with tumor thrombus, which may facilitate ccRCC diagnosis, prognosis and treatment.