Neutral Tumour Evolution Debate

By introducing evolutionary theory methods to the analysis of cancer genomic data, we sparked an intense debate on the extent to which neutral evolution versus subclonal selection explain current data. We argue that both evolutionary regimens manifest at different times during the evolution of the tumour, with selection playing a dominant role in tumour initiation, driving a series of subclonal expansions that lead to the establishment of the malignancy. However, reaching a certain fitness, many but not all cancers continue accumulating mutations under a neutrality regimen, which leaves a specific mark on the distribution of mutations in cancer data. We report below our work as well as the corresponding criticism, including letters and replies that specifically followed our Williams, Werner et al. 2016 work. Enjoy the debate!

Our papers

• Phenotypic plasticity and genetic control in colorectal cancer evolution
  Househam J, Heide T, Cresswell GD, Spiteri I, Kimberley C, Zapata L, Lynn C, James C, Mossner M, Fernandez-Mateos J, Vinceti A, Baker AM, Gabbutt C, Berner A, Schmidt M, Chen B, Lakatos E, Gunasri V, Nichol D, Costa H, Mitchinson M, Ramazzotti D, Werner B, Iorio F, Jansen M, Caravagna G, Barnes C, Shibata D, Bridgewater J, Rodriguez-Justo M, Magnani L, Graham TA, Sottoriva A .
  Nature, 2022.

• Subclonal reconstruction of tumors by using machine learning and population genetics
  Caravagna G, Heide T, Williams MJ, Zapata L, Nichol D, Chkhaidze K, Cross WH, Cresswell GD, Werner B, Acar A, Chesler L, Barnes CP, Sanguinetti G, Graham TA, Sottoriva A. Nature Genetics, 2020, 52:898-907

• Quantification of subclonal selection in cancer from bulk sequencing data
  Williams MJ, Werner B, Heide T, Curtis C, Barnes CP, Sottoriva A, Graham TA. Nature Genetics, 2018, 50(6):895-903.

• Identification of neutral tumor evolution across cancer types
  Williams MJ,Werner B, Barnes CP, Graham TA, Sottoriva A. Nature Genetics, 2016, 48:238-244.

• A Big Bang model of human colorectal tumor growth Sottoriva A, Kang H, Ma Z, Graham TA, Salomon M, Zhao J, Marjoram P, Siegmund K, Press MF, Shibata D, Curtis C. Nature Genetics, 2015, 47 (3): 209-216.

Correspondence (letter and reply)

• Reply to ‘Neutral tumor evolution?’
  Heide T, Zapata L, Williams MJ, Werner B, Barnes CP, Graham TA, Sottoriva A. Nature Genetics, 2018, 50:1633-1637.

• Neutral tumor evolution?
  Tarabichi M, Martincorena I, Gerstung M, Markowetz F, Spellman PT, Morris QD, Lingjaerde OC, Wedge DC, van Loo P. 
  Nature Genetics, 2018, 50:1630-1633.

• Reply to ‘Currently available bulk sequencing data do not necessarily support a model of neutral tumor evolution’
  Werner B, Williams MJ, Barnes CP, Graham TA, Sottoriva A. ​Nature Genetics, 2018, 50:1624-1626.

• Currently available bulk sequencing data do not necessarily support a model of neutral tumor evolution McDonald TO, Chakrabarti S, Michor F. Nature Genetics, 2018, 50:1620-1623.

• Reply to ‘Revisiting signatures of neutral tumor evolution in the light of complexity of cancer genomic data’
  Williams MJ, Werner B, Heide T, Barnes CP, Graham TA, Sottoriva A.
  Nature Genetics, 2018, 50:1628-1630

• Revisiting signatures of neutral tumor evolution in the light of complexity of cancer genomic data
  Balaparya A., De S. Nature Genetics, 2018, 50:1626-1628

• Reply: Uncertainties in tumor allele frequencies limit power to infer evolutionary pressures_
  Williams MJ, Werner B, Barnes CP, Graham TA*, Sottoriva A* Nature Genetics, 2017, 49:1289-1291.

• Uncertainties in tumor allele frequencies limit power to infer evolutionary pressures Noorbakhsh J, Chuang JH.
  Nature Genetics, 2017, 49:1288-1289.

• Reply: Is the evolution in tumors Darwinian or non-Darwinian?
  Williams MJ, Werner B, Barnes CP, Graham TA*, Sottoriva A*. National Science Review, 2018, 5(1):17-19.

• Is the evolution in tumors Darwinian or non-Darwinian? Wang H, Chen Y, Tong D, Ling S, Hu Z, Tao Y, Lu X, Wu C. National Science Review, 2018, 5(1):15-17

From other groups

• Signatures of neutral evolution in exponentially growing tumors: a theoretical perspective Tung HR, Durrett R. PLoS Computational Biology, 2021, 17(2): e1008701.

• Neutral syndrome Leroi AM, Lambert B, Rosindell J, Zhang X, Kokkoris GD.
  Nature Human Behaviour, 2020, 43:1-11.

• Statistical inference for the evolutionary history of cancer genomes Jaksik R, Kimmel M, Lambert A, Tavaré S.
  bioRxiv, 2019, 10.1101/722033.

• On measuring selection in cancer from subclonal mutation frequencies
  Bozic I, Paterson C, Waclaw B.
  PLoS Computational Biology, 2019, 15(9):e1007368.

• An enhanced genetic model of colorectal cancer progression history
  Yang L, Wang S, Lee JJK, Lee S, Lee E, Shinbrot E, Wheeler DA, Kucherlapati R, Park PJ.
  Genome Biology, 2019, 20:168.

• Neutral theory and the somatic evolution of cancer
  Cannataro VL, Townsend JP. Molecular Biology and Evolution, 2018, 36(6):1308-1315.

• Neutral theory in cancer cell population genetic_
  Niida A, Iwasaki WM, Innan H. Molecular Biology and Evolution, 2018, 36(6):1316-1321.

• Quantifying clonal and subclonal passenger mutations in cancer evolution Bozic I, Gerold JM, Nowak MA. PLoS Computational Biology, 2016, 12(2):e1004731.

For a nice recent perspective and overview of the neutral evolution debate in evolutionary biology see recent issue of Molecular Biology and Evolution 2018, Volume 35, Issue 6.