@article{6e82c109ac7b44ada3969c295eb813a1,
title = "DNA Methylation and Somatic Mutations Converge on the Cell Cycle and Define Similar Evolutionary Histories in Brain Tumors",
abstract = "The evolutionary history of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast to stable genetic events, epigenetic states are reversible and sensitive to the microenvironment, prompting the question whether epigenetic information can similarly be used to discover tumor phylogeny. We examined the spatial and temporal dynamics of DNA methylation in a cohort of low-grade gliomas and their patient-matched recurrences. Genes transcriptionally upregulated through promoter hypomethylation during malignant progression to high-grade glioblastoma were enriched in cell cycle function, evolving in parallel with genetic alterations that deregulate the G1/S cell cycle checkpoint. Moreover, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations. These findings highlight widespread co-dependency of genetic and epigenetic events throughout brain tumor evolution.",
author = "Tali Mazor and Aleksandr Pankov and Johnson, {Brett E.} and Chibo Hong and Hamilton, {Emily G.} and Bell, {Robert J.A.} and Smirnov, {Ivan V.} and Reis, {Gerald F.} and Phillips, {Joanna J.} and Barnes, {Michael J.} and Ahmed Idbaih and Agusti Alentorn and Kloezeman, {Jenneke J.} and Lamfers, {Martine L.M.} and Bollen, {Andrew W.} and Taylor, {Barry S.} and Molinaro, {Annette M.} and Olshen, {Adam B.} and Chang, {Susan M.} and Song, {Jun S.} and Costello, {Joseph F.}",
note = "Funding Information: The authors would like to acknowledge R. Nagarajan and S. Fouse for critical discussions, D. Johnson for assistance with mutation validation, N. Jabado and S. Papillon-Cavanagh for providing raw data for methylation analysis, and K. Pollard and her lab for advice on phyloepigenetic evolution analyses. This project was generously supported by Accelerate Brain Cancer Cure and a gift from the Dabbiere family. Additional support was provided by by the National Institute of General Medical Sciences T32GM008568 (to T.M.) and T32GM067547 (to A.P.); the National Science Foundation 1144247 (to A.P.); the National Institutes of Health 1T32CA15102201 (to M.J.B.), R25NS070680 (to M.J.B.), R01CA169316 (to B.S.T and J.F.C.), and P50CA097257 (to J.J.P., B.S.T., A.M.M., S.M.C., and J.F.C.); the National Cancer Institute P30CA82103 (to A.B.O.) and R01CA163336 (to J.S.S.); the Sontag Foundation (to B.S.T. and J.S.S.); and OncoNeuroTh{\`e}que (to A.I. and A.A.). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.",
year = "2015",
month = sep,
day = "14",
doi = "10.1016/j.ccell.2015.07.012",
language = "English (US)",
volume = "28",
pages = "307--317",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}