Abstract 2374: Reconstructing the evolutionary history of metastatic cancers

Johannes G. Reiter, Alvin P. Makohon-Moore, Jeffrey M. Gerold, Ivana Bozic, Krishnendu Chatterjee, Christine A. Iacobuzio-Donahue, Bert Vogelstein, Martin A. Nowak
2016 Cancer Research  
2374: Reconstructing the evolutionary history of metastatic cancers The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications 1-3 . Genome-wide sequencing data has enabled modern phylogenomic methods to accurately dissect subclones and their phylogenies from noisy and impure
more » ... ulk tumor samples at unprecedented depth 4-7 . However, existing methods are not designed to infer metastatic seeding patterns. We have developed a tool, called Treeomics, that utilizes Bayesian inference and Integer Linear Programming to reconstruct the phylogeny of metastases. Treeomics allowed us to infer comprehensive seeding patterns for pancreatic 8 , ovarian 9 , and prostate cancers 10,11 . Moreover, Treeomics correctly disambiguated true seeding patterns from sequencing artifacts; 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumor heterogeneity among distinct samples. Last, we performed in silico benchmarking on simulated tumor phylogenies across a wide range of sample purities (30-90%) and sequencing depths (50-800x) to demonstrate the high accuracy of Treeomics compared to existing methods. Genetic evolution underlies our current understanding of cancer 12-14 and the development of resistance to therapies 15,16 . The principles governing this evolution are still an active area of research, particularly for metastasis, the final biological stage of cancer that is responsible for the vast majority of deaths from the disease. Although many insights into the nature of metastasis have emerged 2,17,18 , we do not yet know how . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a
doi:10.1158/1538-7445.am2016-2374 fatcat:kyyppa6fdbdn5hmjprwlkt4ivu