Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal

PEACE, the TRACERx Renal Consortium

Research output: Contribution to journalArticlepeer-review

413 Scopus citations

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. 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.

Original languageEnglish
Pages (from-to)581-594.e12
JournalCell
Volume173
Issue number3
DOIs
StatePublished - Apr 19 2018

Keywords

  • chromosome instability
  • cytoreductive nephrectomy
  • evolution of metastasis
  • loss of 9p
  • metastasectomy
  • metastasis
  • oligometastasis
  • renal cell cancer
  • solitary metastasis

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