DNA methylation and somatic mutations converge on the cell cycle and define similar evolutionary histories in brain tumors Journal Article
| Authors: | Mazor, T.; Pankov, A.; Johnson, B. E.; Hong, C.; Hamilton, E. G.; Bell, R. J. A.; Smirnov, I. V.; Reis, G. F.; Phillips, J. J.; Barnes, M. J.; Idbaih, A.; Alentorn, A.; Kloezeman, J. J.; Lamfers, M. L. M.; Bollen, A. W.; Taylor, B. S.; Molinaro, A. M.; Olshen, A. B.; Chang, S. M.; Song, J. S.; Costello, J. F. |
| Article 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 G<inf>1</inf>/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. © 2015 Elsevier Inc. |
| Keywords: | human tissue; promoter region; somatic mutation; cancer recurrence; cancer patient; brain tumor; glioma; cancer grading; molecular dynamics; dna methylation; transcription regulation; epigenetics; glioblastoma; upregulation; malignant transformation; cell cycle regulation; transcriptome; molecular phylogeny; tumor microenvironment; g1 phase cell cycle checkpoint; human; priority journal; article; s phase cell cycle checkpoint |
| Journal Title: | Cancer Cell |
| Volume: | 28 |
| Issue: | 3 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2015-09-14 |
| Start Page: | 307 |
| End Page: | 317 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2015.07.012 |
| PROVIDER: | scopus |
| PMCID: | PMC4573399 |
| PUBMED: | 26373278 |
| DOI/URL: | |
| Notes: | Export Date: 2 November 2015 -- Source: Scopus |
