Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal
Copyright policy )Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal
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.
- Institute of Cancer Research United Kingdom
- University College London Hospital United Kingdom
- Washington State University United States
- The Francis Crick Institute
- UCL Hospitals NHS Foundation Trust
Male, cell carcinoma, Biopsy, branched evolution, renal cell cancer, prostate-cancer, loss of 9p, tumor thrombus, pancreatic-cancer, 80 and over, Longitudinal Studies, Prospective Studies, Neoplasm Metastasis, Aged, 80 and over, TUMOR THROMBUS, Chromosome Mapping, CYTOREDUCTIVE NEPHRECTOMY, Middle Aged, PANCREATIC-CANCER, Kidney Neoplasms, PROSTATE-CANCER, oligometastasis, Phenotype, Treatment Outcome, Disease Progression, Female, Chromosomes, Human, Pair 9, Life Sciences & Biomedicine, Human, Pair 9, cytoreductive nephrectomy, EXPRESSION, Adult, Biochemistry & Molecular Biology, SEQUENCING DATA, evolution of metastasis, BRANCHED EVOLUTION, 610, TRACERx Renal Consortium, Chromosomes, Article, PEACE, expression, solitary metastasis, BREAST-CANCER, metastasis, Humans, Carcinoma, Renal Cell, breast-cancer, Aged, Chromosomes, Human, Pair 14, Science & Technology, Pair 14, Carcinoma, sequencing data, Renal Cell, natural-history, Thrombosis, Cell Biology, NATURAL-HISTORY, CELL CARCINOMA, Mutation, chromosome instability, metastasectomy, Biomarkers
Male, cell carcinoma, Biopsy, branched evolution, renal cell cancer, prostate-cancer, loss of 9p, tumor thrombus, pancreatic-cancer, 80 and over, Longitudinal Studies, Prospective Studies, Neoplasm Metastasis, Aged, 80 and over, TUMOR THROMBUS, Chromosome Mapping, CYTOREDUCTIVE NEPHRECTOMY, Middle Aged, PANCREATIC-CANCER, Kidney Neoplasms, PROSTATE-CANCER, oligometastasis, Phenotype, Treatment Outcome, Disease Progression, Female, Chromosomes, Human, Pair 9, Life Sciences & Biomedicine, Human, Pair 9, cytoreductive nephrectomy, EXPRESSION, Adult, Biochemistry & Molecular Biology, SEQUENCING DATA, evolution of metastasis, BRANCHED EVOLUTION, 610, TRACERx Renal Consortium, Chromosomes, Article, PEACE, expression, solitary metastasis, BREAST-CANCER, metastasis, Humans, Carcinoma, Renal Cell, breast-cancer, Aged, Chromosomes, Human, Pair 14, Science & Technology, Pair 14, Carcinoma, sequencing data, Renal Cell, natural-history, Thrombosis, Cell Biology, NATURAL-HISTORY, CELL CARCINOMA, Mutation, chromosome instability, metastasectomy, Biomarkers
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