@article{5b13e3ce561f4743a54c283b1312cf9d,
title = "Punctuated evolution of canonical genomic aberrations in uveal melanoma",
abstract = "Cancer is thought to arise through the accumulation of genomic aberrations evolving under Darwinian selection. However, it remains unclear when the aberrations associated with metastasis emerge during tumor evolution. Uveal melanoma (UM) is the most common primary eye cancer and frequently leads to metastatic death, which is strongly linked to BAP1 mutations. Accordingly, UM is ideally suited for studying the clonal evolution of metastatic competence. Here we analyze sequencing data from 151 primary UM samples using a customized bioinformatic pipeline, to improve detection of BAP1 mutations and infer the clonal relationships among genomic aberrations. Strikingly, we find BAP1 mutations and other canonical genomic aberrations usually arise in an early punctuated burst, followed by neutral evolution extending to the time of clinical detection. This implies that the metastatic proclivity of UM is {"}set in stone{"} early in tumor evolution and may explain why advances in primary treatment have not improved survival.",
author = "Field, {Matthew G.} and Durante, {Michael A.} and Hima Anbunathan and Cai, {Louis Z.} and Decatur, {Christina L.} and Bowcock, {Anne M.} and Stefan Kurtenbach and Harbour, {J. William}",
note = "Funding Information: We are grateful to the patients who generously contributed samples for this research. We thank Lisle Mose and Eric Talevich for their assistance with the ABRA and CNVkit programs, respectively. We acknowledge the support of the Biostatistics & Bioinformatics and Oncogenomics Shared Resources at the Sylvester Comprehensive Cancer Center, and the University of Miami Center for Computational Science. The data used here were generated in part by the TCGA Research Network, Cancer Research UK Manchester Institute, Institut Curie, and University of Duisburg-Essen. This work was supported by National Cancer Institute grants R01 CA125970 (J.W.H.), R01 CA161870 (J.W.H. and A. M.B.) and F30 CA206430 (M.G.F.), Research to Prevent Blindness, Inc. Senior Scientific Investigator Award (J.W.H.), Melanoma Research Foundation (J.W.H. and M.G.F.), Melanoma Research Alliance (J.W.H.), Ocular Melanoma Foundation (J.W.H.), the 2015 RRF/Kayser Global Pan-American Award (J.W.H.), the Alcon Research Institute (J.W. H.), the Sylvester Comprehensive Cancer Center (J.W.H.), the University of Miami Sheila and David Fuente Graduate Program in Cancer Biology (M.G.F. and M.A.D.), the Center for Computational Science Fellowship (M.G.F. and M.A.D.), the AACR-Ocular Melanoma Foundation Fellowship in honor of Robert C. Allen, MD (S.K.), and a generous gift from Dr. Mark J. Daily (J.W.H.). The Bascom Palmer Eye Institute also received funding from NIH Core Grant P30EY014801, Department of Defense Grant #W81XWH-13-1-0048, and a Research to Prevent Blindness Unrestricted Grant. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-017-02428-w",
language = "English (US)",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}