Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.
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Authors
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,
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,
Document Type
Journal Article
Date
2018-04-19
Date Accepted
2018-03-20
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.
Citation
Cell, 2018, 173 (3), pp. 581 - 594.e12
Source Title
Publisher
CELL PRESS
ISSN
0092-8674
eISSN
1097-4172
Research Team
Melanoma and Kidney Cancer
Experimental Pathology
Molecular & Population Genetics
Experimental Pathology
Molecular & Population Genetics