The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen.

Autor:	Malta TM; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Sabedot TS; Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, Michigan., Morosini NS; Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, Michigan., Datta I; Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, Michigan., Garofano L; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida., Vallentgoed W; Neurology Department, The Brain Tumour Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Varn FS; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut., Aldape K; National Cancer Institute, Bethesda, Maryland., D'Angelo F; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida., Bakas S; Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, Pennsylvania.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Barnholtz-Sloan JS; National Cancer Institute, Bethesda, Maryland., Gan HK; Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Melbourne, Australia., Hasanain M; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida., Hau AC; Luxembourg Institute of Health, Luxembourg, Luxembourg., Johnson KC; Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut., Cazacu S; Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, Michigan., deCarvalho AC; Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, Michigan., Khasraw M; Duke University, Durham, North Carolina., Kocakavuk E; Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.; Department of Hematology and Stem Cell Transplantation, West German Cancer Center (WTZ), National Center for Tumor Diseases (NCT) West, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Kouwenhoven MCM; Department of Neurology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands., Migliozzi S; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida., Niclou SP; Luxembourg Institute of Health, Luxembourg, Luxembourg., Niers JM; Department of Neurology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands., Ormond DR; University of Colorado School of Medicine, Department of Neurosurgery, Aurora, Colorado., Paek SH; Department of Neurosurgery, Cancer Research Institute, Hypoxia Ischemia Disease Institute, Seoul National University, Seoul, Republic of Korea (South)., Reifenberger G; Institute of Neuropathology, Heinrich Heine University, Dusseldorf, Germany., Sillevis Smitt PA; Department of Neurology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.; The Brain Tumour Centre, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Smits M; Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands., Stead LF; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., van den Bent MJ; Department of Neurology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.; The Brain Tumour Centre, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Van Meir EG; Department of Neurosurgery and O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama., Walenkamp A; University of Groningen, Groningen, the Netherlands., Weiss T; Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland., Weller M; Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland., Westerman BA; Department of Neurology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands., Ylstra B; Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands., Wesseling P; Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.; Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands.; Laboratory for Childhood Cancer Pathology, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Lasorella A; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida., French PJ; Neurology Department, The Brain Tumour Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Poisson LM; Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, Michigan., Verhaak RGW; Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.; Department of Neurosurgery, Amsterdam University Medical Center, Amsterdam, the Netherlands., Iavarone A; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida., Noushmehr H; Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, Michigan.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2024 Mar 04; Vol. 84 (5), pp. 741-756.
DOI:	10.1158/0008-5472.CAN-23-2093
Abstrakt:	Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histologic progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neoangiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution toward an IDHwt-like phenotype. Significance: Standard treatments are related to loss of DNA methylation in IDHmut glioma, resulting in epigenetic activation of genes associated with tumor progression and alterations in the microenvironment that resemble treatment-naïve IDHwt glioma. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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