Reconstructing metastatic seeding patterns of human cancers Journal Article


Author(s): Reiter, Johannes G; Makohon-Moore, Alvin P; Gerold, Jeffrey M; Božić, Ivana; Chatterjee, Krishnendu; Iacobuzio-Donahue, Christine A; Vogelstein, Bert; Nowak, Martin A
Article Title: Reconstructing metastatic seeding patterns of human cancers
Affiliation IST Austria
Abstract: 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.
Journal Title: Nature Communications
Volume: 8
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2017-01-31
Start Page: Article number: 14114
Copyright Statement: CC BY 4.0
URL:
DOI: 10.1038/ncomms14114
Notes: We thank Marc Attiyeh, Martin Chmelik, Alison Hill and Adeeti Ullal for valuable discussions. This work was supported by the European Research Council (ERC) start grant 279307: Graph Games (J.G.R., C.K.), Austrian Science Fund (FWF) grant no. P23499-N23 (J.G.R., K.C.), FWF NFN grant no. S11407-N23 RiSE/SHiNE (J.G.R., K.C.), a Landry Cancer Biology Fellowship (J.M.G.), National Institutes of Health grants CA179991 (C.A.I.-D., I.B.), F31CA180682 (A.P.M.-M.), CA43460 (B.V.), the Lustgarten Foundation for Pancreatic Cancer Research, The Sol Goldman Center for Pancreatic Cancer Research, The Virginia and D.K. Ludwig Fund for Cancer Research, Office of Naval Research grant N00014-16-1-2914, the Bill and Melinda Gates Foundation OPP1148627, and a gift from B Wu and Eric Larson. Benchmarking was performed on the Odyssey cluster supported by the FAS Division of Science, Research Computing Group at Harvard University.
Open access: yes (OA journal)