Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.


Type
Article
Change log
Authors
Xu, Hang 
Rowan, Andrew 
Chambers, Tim 
Abstract

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.

Description
Keywords
chromosome instability, cytoreductive nephrectomy, evolution of metastasis, loss of 9p, metastasectomy, metastasis, oligometastasis, renal cell cancer, solitary metastasis, Adult, Aged, Aged, 80 and over, Biomarkers, Biopsy, Carcinoma, Renal Cell, Chromosome Mapping, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 9, Disease Progression, Female, Humans, Kidney Neoplasms, Longitudinal Studies, Male, Middle Aged, Mutation, Neoplasm Metastasis, Phenotype, Prospective Studies, Thrombosis, Treatment Outcome
Journal Title
Cell
Conference Name
Journal ISSN
0092-8674
1097-4172
Volume Title
173
Publisher
Elsevier BV
Sponsorship
Medical Research Council (MR/L016311/1)