Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.
Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.
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DOI：
10.1016/j.cell.2018.03.057
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发表时间：
2018-04-19
期刊：
影响因子：
64.5
通讯作者：
TRACERx Renal Consortium
中科院分区：
文献类型：
--
作者：
Turajlic S;Xu H;Litchfield K;Rowan A;Chambers T;Lopez JI;Nicol D;O'Brien T;Larkin J;Horswell S;Stares M;Au L;Jamal-Hanjani M;Challacombe B;Chandra A;Hazell S;Eichler-Jonsson C;Soultati A;Chowdhury S;Rudman S;Lynch J;Fernando A;Stamp G;Nye E;Jabbar F;Spain L;Lall S;Guarch R;Falzon M;Proctor I;Pickering L;Gore M;Watkins TBK;Ward S;Stewart A;DiNatale R;Becerra MF;Reznik E;Hsieh JJ;Richmond TA;Mayhew GF;Hill SM;McNally CD;Jones C;Rosenbaum H;Stanislaw S;Burgess DL;Alexander NR;Swanton C;PEACE;TRACERx Renal Consortium
透明细胞肾细胞癌（ccRCC）表现出广泛的转移表型，迄今尚未进行系统研究。在这里，我们分析了100例转移性ccRCC患者的575例原发性和335例转移性活检，包括两例尸检样本。染色体复杂性提供了转移能力，我们将9p丢失确定为驱动转移和ccRCC相关死亡率的高度选择性事件（p = 0.0014）。观察到不同的转移性播散模式，包括快速进展到多个组织部位，这些组织部位由单克隆结构的原发性肿瘤接种。相比之下，我们观察到在原发肿瘤异质性高的病例中进展减弱，转移能力逐渐获得，最初进展为孤立性转移。最后，我们观察到早期分歧的原始祖先克隆和延长潜伏期长达二十年的胰腺转移的一个特点。来自100例ccRCC病例的匹配原发转移活检的进化研究染色体复杂性提供了转移能力，ccRCC转移的标志性基因组驱动因素是9p和14q的丢失间断和分支演变导致不同的转移模式一项多中心前瞻性研究和两个验证队列，来自100例明确的原发性转移活检患者，细胞肾细胞癌提供了一个全面的图片的遗传基础和演变模式的转移。
Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct patterns of metastatic dissemination were observed, including rapid progression to multiple tissue sites seeded by primary tumors of monoclonal structure. By contrast, we observed attenuated progression in cases characterized by high primary tumor heterogeneity, with metastatic competence acquired gradually and initial progression to solitary metastasis. Finally, we observed early divergence of primitive ancestral clones and protracted latency of up to two decades as a feature of pancreatic metastases. Evolutionary study of matched primary metastasis biopsies from 100 ccRCC cases Metastasis competence is afforded by chromosome complexity, but not driver mutation load The hallmark genomic drivers of ccRCC metastasis are loss of 9p and 14q Punctuated and branched evolution result in distinct patterns of metastases A multi-center prospective study and two validation cohorts of matched primary metastasis biopsies from 100 patients with clear-cell renal cell carcinoma provides a comprehensive picture of the genetic underpinnings and the evolutionary patterns of metastasis.
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影响因子：
64.8
作者：
通讯作者：
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通过BAP1和PBRM1表达鉴定的透明细胞肾细胞癌亚型。
DOI：
10.1016/j.juro.2015.07.113
发表时间：
2016-01
期刊：
The Journal of urology
影响因子：
--
作者：
Joseph RW;Kapur P;Serie DJ;Parasramka M;Ho TH;Cheville JC;Frenkel E;Parker AS;Brugarolas J
通讯作者：
Brugarolas J
影响因子：
7.3
作者：
Bashashati, Ali;Ha, Gavin;Tone, Alicia;Ding, Jiarui;Prentice, Leah M.;Roth, Andrew;Rosner, Jamie;Shumansky, Karey;Kalloger, Steve;Senz, Janine;Yang, Winnie;McConechy, Melissa;Melnyk, Nataliya;Anglesio, Michael;Luk, Margaret T. Y.;Tse, Kane;Zeng, Thomas;Moore, Richard;Zhao, Yongjun;Marra, Marco A.;Gilks, Blake;Yip, Stephen;Huntsman, David G.;McAlpine, Jessica N.;Shah, Sohrab P.
通讯作者：
Shah, Sohrab P.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Field MG;Durante MA;Anbunathan H;Cai LZ;Decatur CL;Bowcock AM;Kurtenbach S;Harbour JW
通讯作者：
Harbour JW