期刊
CELL
卷 173, 期 3, 页码 581-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2018.03.057
关键词
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资金
- Cancer Research UK (CRUK) [C50947/A18176]
- NIH Research (NIHR) Biomedical Research Centre (BRC) at the Royal Marsden Hospital [A109]
- NIH Research (NIHR) Biomedical Research Centre (BRC) at the Institute of Cancer Research [A109]
- Ministerio de Economia y Competitividad (MINECO) [SAF2016-79847-R]
- Royal Marsden Cancer Charity
- UK Medical Research Council [MR/P014712/1, FC001202]
- CRUK
- Rosetrees
- NIHR BRC at University College London Hospitals
- Cancer Research UK (TRACERx)
- Cancer Research UK (CRUK Cancer Immunotherapy Catalyst Network)
- CRUK Lung Cancer Centre of Excellence
- Stand Up 2 Cancer (SU2C)
- Rosetrees Trust
- Stoneygate Trust
- NovoNordisk Foundation [16584]
- Breast Cancer Research Foundation (BCRF)
- European Research Council (THESEUS)
- Marie Curie Network PloidyNet
- CRUK University College London Experimental Cancer Medicine Centre
- Cancer Research UK [C50947/A18176, FC001202]
- Ventana Medical Systems [10467, 10530]
- Kidney Cancer Fund of The Royal Marsden Cancer Charity
- NIHR BRC at the Royal Marsden Hospital [A109]
- NIHR BRC at the Institute of Cancer Research [A109]
- Francis Crick Institute
- Wellcome Trust [FC001202]
- Advanced Sequencing Facility at the Francis Crick Institute
- High-Performance Computing at the Francis Crick Institute
- Medical Research Council [MR/L016311/1]
- Medical Research Council [MR/L016311/1] Funding Source: researchfish
- MRC [MR/P014712/1, MR/L016311/1] Funding Source: UKRI
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.
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