Abstract
Abstract About 50% of renal cell carcinomas (RCCs) progress to the metastatic stage, and become fatal and incurable. Whether such a dismal prognosis is due to early dissemination or late diagnosis of the disease remains unknown. To explore the evolutionary history of metastatic RCC (mRCC), we characterized the genetic, epigenetic and expression profiles of multiple tumors from a mRCC patient, including primary RCC (pRCC), local metastasis in vena cava (MVC) and distant metastasis in brain (MB). Although the multi-omics profiles of bulk tumor tissues differed substantially from each other, quantitative analysis of the multi-level data suggested mRCCs to be resulted from clonal expansion of the rare advantageous subclone developed within the heterogeneous pRCC. Moreover, from the genetic distances between mRCCs and their parental subclone, we estimated that about two and eight years were required for the parental subclone to evolve into progeny subclones that give rise to MVC and MB, respectively. Thus, distant metastasis occurred late during RCC progression and there was a broad window period for early detection of the circulating tumor cells before pRCC acquired full metastatic potential. These findings proved that early detection, followed by early intervention, is possible and necessary for controlling the spread of RCC. Citation Format: Shengjie Gao, Huang Yi, Song Wu, Yuan Yu, Pengfei Song, Guangwu Guo, Xueda Hu. Multiple omics profiling reveals the evolutionary history of metastatic renal cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-230. doi:10.1158/1538-7445.AM2013-LB-230
Published Version
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