Integrative genomic study of Chinese clear cell renal cell carcinoma reveals features associated with thrombus

Xiang-Ming Wang, Yang Lu, Yi-Meng Song, Jun Dong, Ruo-Yan Li, Guo-Liang Wang, Xu Wang, Shu-Dong Zhang, Zhou-Huan Dong, Min Lu, Shi-Yu Wang, Li-Yuan Ge, Guang-Da Luo, Run-Zhuo Ma, Steve George Rozen, Fan Bai (), Di Wu () and Lu-Lin Ma ()
Additional contact information
Xiang-Ming Wang: Peking University
Yang Lu: National Clinical Research Center for Kidney Diseases
Yi-Meng Song: Peking University
Jun Dong: National Clinical Research Center for Kidney Diseases
Ruo-Yan Li: Peking University
Guo-Liang Wang: Peking University
Xu Wang: National Clinical Research Center for Kidney Diseases
Shu-Dong Zhang: Peking University
Zhou-Huan Dong: National Clinical Research Center for Kidney Diseases
Min Lu: Peking University
Shi-Yu Wang: National Clinical Research Center for Kidney Diseases
Li-Yuan Ge: Peking University
Guang-Da Luo: National Clinical Research Center for Kidney Diseases
Run-Zhuo Ma: Peking University
Steve George Rozen: Duke-NUS Medical School
Fan Bai: Peking University
Di Wu: National Clinical Research Center for Kidney Diseases
Lu-Lin Ma: Peking University

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-14601-9

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