Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications. Genome-wide sequencing data has enabled modern phylogenomic methods to accurately dissect subclones and their phylogenies from noisy and impure bulk tumour samples at unprecedented depth. However, existing methods are not designed to infer metastatic seeding patterns. Here we develop a tool, called Treeomics, to reconstruct the phylogeny of metastases and map subclones to their anatomic locations. Treeomics infers comprehensive seeding patterns for pancreatic, ovarian, and prostate cancers. Moreover, Treeomics correctly disambiguates true seeding patterns from sequencing artifacts; 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumour heterogeneity among distinct samples. In silico benchmarking on simulated tumour phylogenies across a wide range of sample purities (15–95%) and sequencing depths (25-800 × ) demonstrates the accuracy of Treeomics compared with existing methods.
Reiter J, Makohon Moore A, Gerold J, et al. Reconstructing metastatic seeding patterns of human cancers. Nature Communications. 2017;8. doi:10.1038/ncomms14114
Reiter, J., Makohon Moore, A., Gerold, J., Božić, I., Chatterjee, K., Iacobuzio Donahue, C., … Nowak, M. (2017). Reconstructing metastatic seeding patterns of human cancers. Nature Communications, 8. https://doi.org/10.1038/ncomms14114
Reiter, Johannes, Alvin Makohon Moore, Jeffrey Gerold, Ivana Božić, Krishnendu Chatterjee, Christine Iacobuzio Donahue, Bert Vogelstein, and Martin Nowak. “Reconstructing Metastatic Seeding Patterns of Human Cancers.” Nature Communications 8 (2017). https://doi.org/10.1038/ncomms14114.
J. Reiter et al., “Reconstructing metastatic seeding patterns of human cancers,” Nature Communications, vol. 8, 2017.
Reiter J, Makohon Moore A, Gerold J, Božić I, Chatterjee K, Iacobuzio Donahue C, Vogelstein B, Nowak M. 2017. Reconstructing metastatic seeding patterns of human cancers. Nature Communications. 8.
Reiter, Johannes, et al. “Reconstructing Metastatic Seeding Patterns of Human Cancers.” Nature Communications, vol. 8, 14114, Nature Publishing Group, 2017, doi:10.1038/ncomms14114.
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