Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study.
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Authors
Fu, X
Zhao, Y
Lopez, JI
Rowan, A
Au, L
Fendler, A
Hazell, S
Xu, H
Horswell, S
Shepherd, STC
Spencer, CE
Spain, L
Byrne, F
Stamp, G
O'Brien, T
Nicol, D
Augustine, M
Chandra, A
Rudman, S
Toncheva, A
Furness, AJS
Pickering, L
Kumar, S
Koh, D-M
Messiou, C
Dafydd, DA
Orton, MR
Doran, SJ
Larkin, J
Swanton, C
Sahai, E
Litchfield, K
Turajlic, S
TRACERx Renal Consortium,
Bates, PA
Zhao, Y
Lopez, JI
Rowan, A
Au, L
Fendler, A
Hazell, S
Xu, H
Horswell, S
Shepherd, STC
Spencer, CE
Spain, L
Byrne, F
Stamp, G
O'Brien, T
Nicol, D
Augustine, M
Chandra, A
Rudman, S
Toncheva, A
Furness, AJS
Pickering, L
Kumar, S
Koh, D-M
Messiou, C
Dafydd, DA
Orton, MR
Doran, SJ
Larkin, J
Swanton, C
Sahai, E
Litchfield, K
Turajlic, S
TRACERx Renal Consortium,
Bates, PA
Document Type
Journal Article
Date
2022-01-01
Date Accepted
2021-10-07
Abstract
Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant clonal dynamics remain limited. We investigated spatial and temporal features of clonal diversification in clear cell renal cell carcinoma through a combination of modelling and real tumour analysis. We observe that the mode of tumour growth, surface or volume, impacts the extent of subclonal diversification, enabling interpretation of clonal diversity in patient tumours. Specific patterns of proliferation and necrosis explain clonal expansion and emergence of parallel evolution and microdiversity in tumours. In silico time-course studies reveal the appearance of budding structures before detectable subclonal diversification. Intriguingly, we observe radiological evidence of budding structures in early-stage clear cell renal cell carcinoma, indicating that future clonal evolution may be predictable from imaging. Our findings offer a window into the temporal and spatial features of clinically relevant clonal evolution.
Citation
Nature ecology & evolution, 2022, 6 (1), pp. 88 - 102
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2397-334X
eISSN
2397-334X
2397-334X
2397-334X
Research Team
Melanoma and Kidney Cancer
Experimental Pathology
Magnetic Resonance
Experimental Pathology
Magnetic Resonance