Clonal architectures predict clinical outcome in clear cell renal cell carcinoma

• Published in: Nature communications Vol. 10; no. 1; p. 1245
• Main Authors: Huang, Yi, Wang, Jiayin, Jia, Peilin, Li, Xiangchun, Pei, Guangsheng, Wang, Changxi, Fang, Xiaodong, Zhao, Zhongming, Cai, Zhiming, Yi, Xin, Wu, Song, Zhang, Baifeng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.03.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 45/23; 45/91; 631/67/2329; 631/67/589/1588/1351; 631/67/69; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Clear cell-type renal cell carcinoma; Clinical outcomes; Clone Cells - immunology; Clone Cells - metabolism; Cohort Studies; Copy number; DNA Copy Number Variations - genetics; DNA-Binding Proteins; Evolution; Evolution, Molecular; Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Genital cancers; Helper cells; Humanities and Social Sciences; Humans; Kidney - pathology; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - immunology; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Lymphocytes; Lymphocytes T; multidisciplinary; Mutation; Nuclear Proteins - genetics; Patients; Populations; Prognosis; Science; Science (multidisciplinary); Survival Analysis; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Th2 Cells - immunology; Transcription Factors - genetics; VHL protein; Von Hippel-Lindau Tumor Suppressor Protein - genetics; Whole Genome Sequencing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09241-7

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: VHL and PBRM1 mutations, 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 with VHL but depleted of BAP1 mutations, 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. Clear cell renal cell carcinoma (ccRCC) is a urogenital cancer with a well-defined genetic landscape. Here, the authors analyse the clonal architecture of ccRCC patients from three populations, and find prognostic subtypes linked to immune infiltrates and clonal architecture.