Citations 1
Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma
Sun, Guangxi , Liang, Jiayu, Yin, Xiaoxue , Zhang, Mengni , Yao, Jin , He, Ning , Armstrong, Cameron M. , Zheng, Linmao , Sun, Xiaomeng , Yang, Xiaoxia , Zhao, Wanbin , Liao, Banghua , Pan, Xiuyi , Yang, Ling , Zhao, Jinge , Dai, Jindong, Shen, Yali , Huang, Rui , Liu, Jiandong , Wang, Zhipeng , Ni, Yuchao , Wei, Qiang , Zhou, Qiao , Liu, Zhenhua , Shen, Pengfei , Chen, Ni , Zeng, Hao , Sun, Guangxi , Chen, Junru , Zhang, Xingming , Zhu, Sha , Nie, Ling , Chen, Yahong , Zhang, Haoran , Liu, Jiyan , Li, Xiang , Huang, Haojie
No container title available | March 11, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer that has no standard treatment for advanced disease. We described 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, certain fusion isoforms and high somatic copy number alteration burdens were associated with aggressive features and poor outcomes. Apart from tumors with MED15-TFE3 fusion, most TFE3-tRCCs exhibited low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis revealed five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which showed association with fusion patterns and prognosis. Specifically, the high angiogenesis/stroma/proliferation cluster exclusively consisted of tumors with ASPSCR1-TFE3 fusion, which was likely to benefit from combination of immune checkpoint and anti-angiogenesis inhibitors. Our findings reveal the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease.