机构：[1]Department of Urology, Peking University First Hospital, Beijing 100034, China[2]Institution of Urology, Peking University, Beijing 100034, China[3]Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing 100034, China[4]National Urological Cancer Center, Beijing 100034, China[5]Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, and China National Center for Bioinformation, Chinese Academy of Sciences, Beijing 100101, China[6]University of Chinese Academy of Sciences, Beijing 100049, China[7]Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China[8]Department of Urology,Beijing Tongren Hospital,Capital Medical University,No. 1 Dongjiaomingxiang Street,Dongcheng District,Beijing 100730,China首都医科大学附属北京同仁医院首都医科大学附属同仁医院临床科室泌尿外科
BackgroundVon Hippel-Lindau (VHL) disease is an autosomal dominant hereditary tumor syndrome with an incidence of approximately 1/36,000. VHL disease-associated clear cell renal cell carcinoma (ccRCC) is the most common congenital RCC. Although recent advances in treating RCC have improved the long-term prognosis of patients with VHL disease, kidney cancer is still the leading cause of death in these patients. Therefore, finding new targets for diagnosing and treating VHL disease-associated ccRCC is still essential.MethodsIn this study, we collected matched tumor tissues and normal samples from 25 patients with VHL disease-associated ccRCC, diagnosed and surgically treated in the Department of Urology, Peking University First Hospital. After screening, we performed whole genome bisulfite sequencing (WGBS) on 23 pairs of tissues and RNA-seq on 6 pairs of tissues. And we also compared the VHL disease-associated ccRCC transcriptome data with the sporadic ccRCC transcriptome data from the The Cancer Genome Atlas (TCGA) public databaseResultsWe found that the methylation level of VHL disease-associated ccRCC tumor tissues was significantly lower than that of normal tissues. The tumor tissues showed a difference in the copy number of 3p loss and 5q and 7q gain compared with normal tissues. We integrated RNA-seq and WGBS data to reveal methylation candidate genes associated with VHL disease-associated ccRCC; our results showed 124 hypermethylated and downregulated genes, and 245 hypomethylated and upregulated genes. By comparing the VHL disease-associated ccRCC transcriptome data with the sporadic ccRCC transcriptome data from the TCGA public database, we found that the major pathways of differential gene enrichment differed between them.ConclusionsOur study mapped the multiomics of copy number variation, methylation and mRNA level changes in tumor and normal tissues of clear cell renal cell carcinoma with VHL syndrome, which provides a solid foundation for the mechanistic study, biomarker screening, and therapeutic target discovery of clear cell renal cell carcinoma.
基金：
National High-Level Hospital
Clinical Research Funding (High-Quality Clinical Research Project of
Peking University First Hospital, 2022CR75), National Natural Science
Foundation of China (no. 82141103; 82172617; 82172665; 81872081),
Scientifc Research Seed Fund of Peking University First Hospital
(2021SF01; 2023SF40), Capital’s Funds for Health Improvement and
Research (2022-2-4074), and Sino-Russian Mathematics Center.
第一作者机构：[1]Department of Urology, Peking University First Hospital, Beijing 100034, China[2]Institution of Urology, Peking University, Beijing 100034, China[3]Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing 100034, China[4]National Urological Cancer Center, Beijing 100034, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Urology, Peking University First Hospital, Beijing 100034, China[2]Institution of Urology, Peking University, Beijing 100034, China[3]Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing 100034, China[4]National Urological Cancer Center, Beijing 100034, China[5]Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, and China National Center for Bioinformation, Chinese Academy of Sciences, Beijing 100101, China[6]University of Chinese Academy of Sciences, Beijing 100049, China[7]Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
推荐引用方式(GB/T 7714)：
Li Lei,Bao Hainan,Xu Yawei,et al.Preliminary Study of Whole-Genome Bisulfite Sequencing and Transcriptome Sequencing in VHL Disease-Associated ccRCC[J].MOLECULAR DIAGNOSIS & THERAPY.2023,27(6):741-752.doi:10.1007/s40291-023-00663-0.
APA：
Li, Lei,Bao, Hainan,Xu, Yawei,Yang, Wuping,Zhang, Zedan...&Gong, Kan.(2023).Preliminary Study of Whole-Genome Bisulfite Sequencing and Transcriptome Sequencing in VHL Disease-Associated ccRCC.MOLECULAR DIAGNOSIS & THERAPY,27,(6)
MLA：
Li, Lei,et al."Preliminary Study of Whole-Genome Bisulfite Sequencing and Transcriptome Sequencing in VHL Disease-Associated ccRCC".MOLECULAR DIAGNOSIS & THERAPY 27..6(2023):741-752
