Details

Autor(en) / Beteiligte

• Mazor, Tali
• Pankov, Aleksandr
• Johnson, Brett E.
• Hong, Chibo
• Hamilton, Emily G.
• Bell, Robert J.A.
• Smirnov, Ivan V.
• Reis, Gerald F.
• Phillips, Joanna J.
• Barnes, Michael J.
• Idbaih, Ahmed
• Alentorn, Agusti
• Kloezeman, Jenneke J.
• Lamfers, Martine L.M.
• Bollen, Andrew W.
• Taylor, Barry S.
• Molinaro, Annette M.
• Olshen, Adam B.
• Chang, Susan M.
• Song, Jun S.
• Costello, Joseph F.

Titel

DNA Methylation and Somatic Mutations Converge on the Cell Cycle and Define Similar Evolutionary Histories in Brain Tumors

Ist Teil von

• Cancer cell, 2015-09, Vol.28 (3), p.307-317

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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. [Display omitted] •Dramatic loss of DNA methylation during the progression of low-grade gliomas to GBM•Phenotypic convergence of genomic and epigenomic evolution on cell cycle defects•Phyloepigenetics recapitulates the phylogenetics of tumor evolution•Robust model of gliomagenesis from tumor initiation through malignant progression Mazor et al. show that spatial and temporal patterns of DNA methylation and somatic mutations during the progression of low-grade gliomas to high-grade tumors produce remarkably similar evolutionary histories and both converge to deregulate the cell cycle.