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Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study.

Xiao FuYue ZhaoJose I LopezAndrew RowanLewis AuAnnika FendlerSteve HazellHang XuStuart HorswellScott T C ShepherdCharlotte E SpencerLavinia SpainFiona ByrneGordon W H StampTim O'BrienDavid NicolMarcellus AugustineAshish ChandraSarah RudmanAntonia TonchevaAndrew J S FurnessLisa M PickeringSantosh KumarDow-Mu KohChristina MessiouDerfel Ap DafyddMatthew R OrtonSimon J DoranJames LarkinCharles SwantonErik SahaiKevin LitchfieldSamra Turajlicnull nullPaul A Bates
Published in: Nature ecology & evolution (2021)
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.
Keyphrases
  • early stage
  • high resolution
  • signaling pathway
  • squamous cell carcinoma
  • single cell
  • neoadjuvant chemotherapy
  • single molecule