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学科主题: 临床医学
题名:
Multilayered molecular profiling supported the monoclonal origin of metastatic renal cell carcinoma
作者: Huang, Yi1,2; Gao, Shengjie3; Wu, Song1,2,4; Song, Pengfei3; Sun, Xiaojuan1,2; Hu, Xueda3; Zhang, Shiqiang5; Yu, Yuan3; Zhu, Jialou3; Li, Cailing5; Qin, Zike4; Xie, Liangfu5; Yao, Qiong3; Tang, Aifa1,2; Li, Zesong1,2; Guo, Guangwu3; Wan, Shengqing3; Dong, Pei4; Sun, Liang1; Li, Weiping1; Wang, Daping1; Gui, Yaoting5; Yang, Huanming3; Zhou, Fangjian4; Zhang, Xiuqing3; Cai, Zhiming1,2
关键词: renal cancer ; tumor evolution ; metastasis
刊名: INTERNATIONAL JOURNAL OF CANCER
发表日期: 2014-07-01
DOI: 10.1002/ijc.28654
卷: 135, 期:1, 页:78-87
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: PROSTATE-CANCER ; GENE ; EVOLUTION ; TUMORS ; P85-ALPHA ; MUTATION ; OVARIAN ; GENOME
英文摘要:

Primary renal cell carcinomas (pRCCs) have a high degree of intratumoral heterogeneity and are composed of multiple distinct subclones. However, it remains largely unknown that whether metastatic renal cell carcinomas (mRCCs) also have startling intratumoral heterogeneity or whether development of mRCCs is due to early dissemination or late diagnosis. To decipher the evolution of mRCC, we analyzed the multilayered molecular profiles of pRCC, local invasion of the vena cava (IVC), and distant metastasis to the brain (MB) from the same patient using whole-genome sequencing, whole-exome sequencing, DNA methylome profiling, and transcriptome sequencing. We found that mRCC had a lower degree of heterogeneity than pRCC and was likely to result from recent clonal expansion of a rare, advantageous subclone. Consequently, some key pathways that are targeted by clinically available drugs showed distinct expression patterns between pRCC and mRCC. From the genetic distances between different tumor subclones, we estimated that the progeny subclone giving rise to distant metastasis took over half a decade to acquire the full potential of metastasis since the birth of the subclone that evolved into IVC. Our evidence supported that mRCC was monoclonal and distant metastasis occurred late during renal cancer progression. Thus, there was a broad window for early detection of circulating tumor cells and future targeted treatments for patients with mRCCs should rely on the molecular profiles of metastases.

语种: 英语
所属项目编号: 81272840 ; 81201579 ; 81301740 ; 81071704 ; JCYJ20130401114928183 ; JCYJ20130401114715714
项目资助者: National Natural Science Foundation of China ; Young Scientists Fund of the National Natural Science Foundation of China ; Shenzhen Basic Research Project ; Shenzhen Knowledge Innovation Project
WOS记录号: WOS:000334353500009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52056
Appears in Collections:北京大学深圳医院_期刊论文

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作者单位: 1.BGI Shenzhen, Shenzhen, Peoples R China
2.Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Shenzhen 518035, Peoples R China
3.Shenzhen Key Lab Genitourinary Tumor, Natl Reg Key Technol Engn Lab Clin Applicat Canc, Shenzhen, Peoples R China
4.Sun Yat Sen Univ, Ctr Canc, Dept Urol, Guangzhou 510275, Guangdong, Peoples R China
5.Peking Univ, Shenzhen Hosp, Shenzhen PKU HKUST Med Ctr,Inst Pathol, Guangdong & Shenzhen Key Lab Male Reprod Med & Ge, Shenzhen, Peoples R China

Recommended Citation:
Huang, Yi,Gao, Shengjie,Wu, Song,et al. Multilayered molecular profiling supported the monoclonal origin of metastatic renal cell carcinoma[J]. INTERNATIONAL JOURNAL OF CANCER,2014,135(1):78-87.
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