Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.
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Date
2018-04-19Author
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,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
PEACE
TRACERx Renal Consortium
Chromosomes, Human, Pair 9
Chromosomes, Human, Pair 14
Humans
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasm Metastasis
Thrombosis
Disease Progression
Biopsy
Treatment Outcome
Longitudinal Studies
Prospective Studies
Chromosome Mapping
Phenotype
Mutation
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Biomarkers
Research team
Melanoma and Kidney Cancer
Experimental Pathology
Molecular & Population Genetics
Language
eng
Date accepted
2018-03-20
License start date
2018-04-12
Citation
Cell, 2018, 173 (3), pp. 581 - 594.e12
Publisher
CELL PRESS