Citations 2
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.
Integrated Molecular Characterization of Fumarate Hydratase–deficient Renal Cell Carcinoma
Sun, Guangxi , Liang, Jiayu, Pan, Xiuyi , Zhu, Sha , Liu, Zhenhua, Armstrong, Cameron M. , Lin, Wei, Liao, Banghua , Lin, Tianhai , Zhang, Mengni , Zheng, Linmao , Yin, Xiaoxue , Shen, Pengfei , Zhao, Jinge , Dai, Jindong, Shen, Yali, Li, Zhiping , Liu, Jiyan , Chen, Junru , Ni, Yuchao , Qin, Dan , Yang, Ling , Wei, Qiang , Li, Xiang , Zhou, Qiao , Yao, Jin , Chen, Ni , Zeng, Hao , Wang, Zhipeng , Liu, Zhenhua , Huang, Rui , Shen, Pengfei , Zhu, Sha , Chen, Junru , Wang, Zhipeng , Zhang, Xingming , Chen, Jianhui , Lin, Wei, Nie, Ling , Zhang, Haoran , Wang, Zhipeng , Zhu, Xudong , Chen, Yahong , Huang, Haojie
Clinical Cancer Research | January 7, 2021 | Volume: 27 | Issue: 6 | Pages: 1734-1743
AbstractPurpose:Fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) is a rare but lethal subtype of RCC. Little is known about the genomic profile of FH-deficient RCC, and the therapeutic options for advanced disease are limited. To this end, we performed a comprehensive genomics study to characterize the genomic and epigenomic features of FH-deficient RCC.Experimental Design:Integrated genomic, epigenomic, and molecular analyses were performed on 25 untreated primary FH-deficient RCCs. Complete clinicopathologic and follow-up data of these patients were recorded.Results:We identified that FH-deficient RCC manifested low somatic mutation burden (median 0.58 mutations per megabase), but with frequent somatic copy-number alterations. The majority of FH-deficient RCCs were characterized by a CpG sites island methylator phenotype, displaying concerted hypermethylation at numerous CpG sites in genes of transcription factors, tumor suppressors, and tumor hallmark pathways. However, a few cases (20%) with low metastatic potential showed relatively low DNA methylation levels, indicating the heterogeneity of methylation pattern in FH-deficient RCC. Moreover, FH-deficient RCC is potentially highly immunogenic, characterized by increased tumor T-cell infiltration but high expression of immune checkpoint molecules in tumors. Clinical data further demonstrated that patients receiving immune checkpoint blockade–based treatment achieved improved progression-free survival over those treated with antiangiogenic monotherapy (median, 13.3 vs. 5.1 months; P = 0.03).Conclusions:These results reveal the genomic features and provide new insight into potential therapeutic strategies for FH-deficient RCC.