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Multisite tumor sampling enhances the detection of intratumor heterogeneity at all different temporal stages of tumor evolution


Intratumor heterogeneity (ITH) is an inherent process of tumor development that has received much attention in previous years, as it has become a major obstacle for the success of targeted therapies. ITH is also temporally unpredictable across tumor evolution, which makes its precise characterization even more problematic since detection success depends on the precise temporal snapshot at which ITH is analyzed. New and more efficient strategies for tumor sampling are needed to overcome these difficulties which currently rely entirely on the pathologist’s interpretation. Recently, we showed that a new strategy, the multisite tumor sampling, works better than the routine sampling protocol for the ITH detection when the tumor time evolution was not taken into consideration. Here, we extend this work and compare the ITH detections of multisite tumor sampling and routine sampling protocols across tumor time evolution, and in particular, we provide in silico analyses of both strategies at early and late temporal stages for four different models of tumor evolution (linear, branched, neutral, and punctuated). Our results indicate that multisite tumor sampling outperforms routine protocols in detecting ITH at all different temporal stages of tumor evolution. We conclude that multisite tumor sampling is more advantageous than routine protocols in detecting intratumor heterogeneity.

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All the authors acknowledge the following:

1. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work.

2. Drafting the work or revising it critically for important intellectual content.

3. Final approval of the version to be published.

4. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to José I. López.

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This is an in silico work not involving human participants neither animals.

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The authors declare no conflict of interest

Electronic Supplementary Materials


Fig. S1 (supplemental figure): Animated gif showing the time evolution of Fig. 3. (GIF 7374 kb)

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Erramuzpe, A., Cortés, J.M. & López, J.I. Multisite tumor sampling enhances the detection of intratumor heterogeneity at all different temporal stages of tumor evolution. Virchows Arch 472, 187–194 (2018).

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  • Tumor sampling
  • Personalized
  • Intratumor heterogeneity
  • Tumor evolution
  • In silico analysis
  • Divide and conquer algorithm
  • Personalized therapy