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Series GSE248471 Query DataSets for GSE248471
Status Public on Dec 13, 2023
Title The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen
Organism Homo sapiens
Experiment type Methylation profiling by array
Methylation profiling by genome tiling array
Summary 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 histological 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 neo-angiogenesis 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 towards an IDHwt-like phenotype.
 
Overall design The GLASS epigenomic cohort consists of 357 DNA methylation samples profiled by either Illumina 450K or EPIC Beadchip methylation arrays. Newly generated DNA methylation data was collected from four different institutions: Henry Ford Hospital (N=103), University of Leeds (UK) (N=8), Chinese University of Hong Kong (N=6), and Luxembourg Institute of Health (N=54) and is available in this series. Previously published data is not included here (they can be accessed at:EGAS00001001255, EGAS00001001854, and EGAS00001001588 .
 
Contributor(s) Malta TM, Datta I, Poisson LM
Citation(s) 38117484
Submission date Nov 22, 2023
Last update date Mar 13, 2024
Contact name Laila M Poisson
E-mail(s) lpoisso1@hfhs.org
Organization name Henry Ford Health
Street address 2799 W Grand Blvd
City Detroit
State/province MI
ZIP/Postal code 48202
Country USA
 
Platforms (2)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
GPL21145 Infinium MethylationEPIC
Samples (245)
GSM7915078 glioma_Recurrence 1 [GLSS-FG-0001-R1-01M-450-AED962]
GSM7915079 glioma_Primary [GLSS-FG-0001-TP-01M-450-754721]
GSM7915080 glioma_Primary [GLSS-FG-0001-TP-02M-450-D60E26]
Relations
BioProject PRJNA1044103

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE248471_RAW.tar 3.2 Gb (http)(custom) TAR (of IDAT)
GSE248471_beta_450GLASS.csv.gz 166.7 Mb (ftp)(http) CSV
GSE248471_beta_MergedGLASS.csv.gz 450.0 Mb (ftp)(http) CSV
GSE248471_beta_epicGLASS.csv.gz 581.1 Mb (ftp)(http) CSV

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