Integrated Molecular Characterization of Fumarate Hydratase-deficient Renal Cell Carcinoma.

Autor:	Sun G; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Zhang X; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Liang J; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Pan X; Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Zhu S; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Liu Z; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Armstrong CM; Department of Urology and Comprehensive Cancer Center, University of California Davis, Sacramento, California., Chen J; Department of Urology, Fujian Medical University Union Hospital, Fuzhou, Fujian, P.R. China., Lin W; Department of Urology, Zigong Fourth People's Hospital, Zigong, Sichuan, P.R. China., Liao B; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Lin T; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Huang R; Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Zhang M; Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Zheng L; Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Yin X; Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Nie L; Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Shen P; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Zhao J; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Zhang H; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Dai J; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Shen Y; Department of Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Li Z; Department of Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Liu J; Department of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Chen J; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Liu J; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.; Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China., Wang Z; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Zhu X; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Ni Y; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Qin D; The Bioinformatics Department, Basebiotech Co., Ltd, Chengdu, P.R. China., Yang L; Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Chen Y; Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Wei Q; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Li X; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Zhou Q; Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China., Huang H; Departments of Biochemistry and Molecular Biology and Urology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota., Yao J; Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China. kucaizeng@163.com chenni1@163.com shelleyyao@163.com., Chen N; Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China. kucaizeng@163.com chenni1@163.com shelleyyao@163.com., Zeng H; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China. kucaizeng@163.com chenni1@163.com shelleyyao@163.com.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Mar 15; Vol. 27 (6), pp. 1734-1743. Date of Electronic Publication: 2021 Jan 07.
DOI:	10.1158/1078-0432.CCR-20-3788
Abstrakt:	Purpose: 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. (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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