Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma

Guangxi Sun; Junru Chen; Jiayu Liang; Xiaoxue Yin; Mengni Zhang; Jin Yao; Ning He; Cameron M. Armstrong; Linmao Zheng; Xingming Zhang; Sha Zhu; Xiaomeng Sun; Xiaoxia Yang; Wanbin Zhao; Banghua Liao; Xiuyi Pan; Ling Nie; Ling Yang; Yuntian Chen; Jinge Zhao; Haoran Zhang; Jindong Dai; Yali Shen; Jiyan Liu; Rui Huang; Jiandong Liu; Zhipeng Wang; Yuchao Ni; Qiang Wei; Xiang Li; Qiao Zhou; Haojie Huang; Zhenhua Liu; Pengfei Shen; Ni Chen; Hao Zeng

doi:10.1038/s41467-021-25618-z

Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma

Guangxi Sun, Junru Chen, Jiayu Liang, Xiaoxue Yin, Mengni Zhang, Jin Yao, Ning He, Cameron M. Armstrong, Linmao Zheng, Xingming Zhang, Sha Zhu, Xiaomeng Sun, Xiaoxia Yang, Wanbin Zhao, Banghua Liao, Xiuyi Pan, Ling Nie, Ling Yang, Yuntian Chen, Jinge ZhaoHaoran Zhang, Jindong Dai, Yali Shen, Jiyan Liu, Rui Huang, Jiandong Liu, Zhipeng Wang, Yuchao Ni, Qiang Wei, Xiang Li, Qiao Zhou, Haojie Huang, Zhenhua Liu, Pengfei Shen, Ni Chen, Hao Zeng

Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	5262
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-25618-z
State	Published - Dec 1 2021

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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Sun, G., Chen, J., Liang, J., Yin, X., Zhang, M., Yao, J., He, N., Armstrong, C. M., Zheng, L., Zhang, X., Zhu, S., Sun, X., Yang, X., Zhao, W., Liao, B., Pan, X., Nie, L., Yang, L., Chen, Y., ... Zeng, H. (2021). Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma. Nature communications, 12(1), Article 5262. https://doi.org/10.1038/s41467-021-25618-z

Sun, G, Chen, J, Liang, J, Yin, X, Zhang, M, Yao, J, He, N, Armstrong, CM, Zheng, L, Zhang, X, Zhu, S, Sun, X, Yang, X, Zhao, W, Liao, B, Pan, X, Nie, L, Yang, L, Chen, Y, Zhao, J, Zhang, H, Dai, J, Shen, Y, Liu, J, Huang, R, Liu, J, Wang, Z, Ni, Y, Wei, Q, Li, X, Zhou, Q, Huang, H, Liu, Z, Shen, P, Chen, N & Zeng, H 2021, 'Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma', Nature communications, vol. 12, no. 1, 5262. https://doi.org/10.1038/s41467-021-25618-z

@article{8e40a4cdaa0c4b7d8338e7160be8e476,

title = "Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma",

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.",

author = "Guangxi Sun and Junru Chen and Jiayu Liang and Xiaoxue Yin and Mengni Zhang and Jin Yao and Ning He and Armstrong, {Cameron M.} and Linmao Zheng and Xingming Zhang and Sha Zhu and Xiaomeng Sun and Xiaoxia Yang and Wanbin Zhao and Banghua Liao and Xiuyi Pan and Ling Nie and Ling Yang and Yuntian Chen and Jinge Zhao and Haoran Zhang and Jindong Dai and Yali Shen and Jiyan Liu and Rui Huang and Jiandong Liu and Zhipeng Wang and Yuchao Ni and Qiang Wei and Xiang Li and Qiao Zhou and Haojie Huang and Zhenhua Liu and Pengfei Shen and Ni Chen and Hao Zeng",

note = "Funding Information: The authors thank all patients involved in this study, as well as their families/caregivers. We offer sincere gratitude to Prof. Allen C. Gao from UC Davis Medical Center for the constructive suggestions and careful revision for this manuscript. Thanks to Mrs. Dan Qin from basebiotech Co., Ltd and Ph.D Menghuan Zhang from GloriousMed Clinical Laboratory (Shanghai) Co., Ltd for providing help for bioinformatic analysis and raw data uploading. This work was supported by the Natural Science Foundation of China (NSFC 81972502, 81902577, 81974398,81872107 and 81872108), China Postdoctoral Science Foundation (2020M673239), Research Foundation for the Postdoctoral Program of Sichuan University (2021SCU12014), Post-Doctor Research Project, West China Hospital, Sichuan University (20HXBH026), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (No.0040205301E21), and Science and Technology Support Program of Sichuan Province (2021YFS0119). Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-021-25618-z",

language = "English (US)",

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journal = "Nature communications",

issn = "2041-1723",

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T1 - Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma

AU - Sun, Guangxi

AU - Chen, Junru

AU - Liang, Jiayu

AU - Yin, Xiaoxue

AU - Zhang, Mengni

AU - Yao, Jin

AU - He, Ning

AU - Armstrong, Cameron M.

AU - Zheng, Linmao

AU - Zhang, Xingming

AU - Zhu, Sha

AU - Sun, Xiaomeng

AU - Yang, Xiaoxia

AU - Zhao, Wanbin

AU - Liao, Banghua

AU - Pan, Xiuyi

AU - Nie, Ling

AU - Yang, Ling

AU - Chen, Yuntian

AU - Zhao, Jinge

AU - Zhang, Haoran

AU - Dai, Jindong

AU - Shen, Yali

AU - Liu, Jiyan

AU - Huang, Rui

AU - Liu, Jiandong

AU - Wang, Zhipeng

AU - Ni, Yuchao

AU - Wei, Qiang

AU - Li, Xiang

AU - Zhou, Qiao

AU - Huang, Haojie

AU - Liu, Zhenhua

AU - Shen, Pengfei

AU - Chen, Ni

AU - Zeng, Hao

N1 - Funding Information: The authors thank all patients involved in this study, as well as their families/caregivers. We offer sincere gratitude to Prof. Allen C. Gao from UC Davis Medical Center for the constructive suggestions and careful revision for this manuscript. Thanks to Mrs. Dan Qin from basebiotech Co., Ltd and Ph.D Menghuan Zhang from GloriousMed Clinical Laboratory (Shanghai) Co., Ltd for providing help for bioinformatic analysis and raw data uploading. This work was supported by the Natural Science Foundation of China (NSFC 81972502, 81902577, 81974398,81872107 and 81872108), China Postdoctoral Science Foundation (2020M673239), Research Foundation for the Postdoctoral Program of Sichuan University (2021SCU12014), Post-Doctor Research Project, West China Hospital, Sichuan University (20HXBH026), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (No.0040205301E21), and Science and Technology Support Program of Sichuan Province (2021YFS0119). Publisher Copyright: © 2021, The Author(s).

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

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JO - Nature communications

JF - Nature communications

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ER -

Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma

Abstract

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