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- Title
Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma.
- Authors
Sun, Guangxi; Chen, Junru; Liang, Jiayu; Yin, Xiaoxue; Zhang, Mengni; Yao, Jin; He, Ning; Armstrong, Cameron M.; Zheng, Linmao; Zhang, Xingming; Zhu, Sha; Sun, Xiaomeng; Yang, Xiaoxia; Zhao, Wanbin; Liao, Banghua; Pan, Xiuyi; Nie, Ling; Yang, Ling; Chen, Yuntian; Zhao, Jinge
- Abstract
TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer with no standard treatment for advanced disease. We describe comprehensive molecular characteristics of 63 untreated primary TFE3-tRCCs based on whole-exome and RNA sequencing. TFE3-tRCC is highly heterogeneous, both clinicopathologically and genotypically. ASPSCR1-TFE3 fusion and several somatic copy number alterations, including the loss of 22q, are associated with aggressive features and poor outcomes. Apart from tumors with MED15-TFE3 fusion, most TFE3-tRCCs exhibit low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis reveals five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which show association with fusion patterns and prognosis. In line with the aggressive nature, the high angiogenesis/stroma/proliferation cluster exclusively consists of tumors with ASPSCR1-TFE3 fusion. Here, we describe the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease. TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare subtype of kidney cancer with no standard treatment options for the advanced disease. Here, the authors perform genomic and transcriptomic profiling of 63 untreated primary TFE3-tRCC tumours and reveal potential therapeutic targets.
- Subjects
RENAL cell carcinoma; RNA sequencing; MOLECULAR clusters; RENAL cancer; DRUG target; PROGRAMMED cell death 1 receptors
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-25618-z