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| Status |
Public on Mar 04, 2024 |
| Title |
Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Other
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| Summary |
Atypical teratoid/rhabdoid tumors (AT/RTs) are pediatric brain tumors known for their aggressiveness, exceptionally low mutation rate, and aberrant but still unresolved epigenetic regulation. To evaluate methylation associated regulation in AT/RTs, we compared them to medulloblastomas and choroid plexus tumors by integrating DNA methylation (507 samples), gene expression (120 samples), and public transcription factor (TF) binding data. We showed that elevated DNA methylation masks the binding sites of TFs driving neural development and is associated with reduced transcription for specific neural regulators in AT/RTs. Hypermethylated sites largely behaved similarly in AT/RTs and pluripotent stem cells, revealing DNA methylation -driven halted cell differentiation. AT/RT-unique DNA hypermethylation was associated with polycomb repressive complex 2 members, like EZH2, and linked to suppressed genes with a role in neural development and tumorigenesis. The obtained results highlight and characterize these DNA methylation programs as drivers of AT/RT malignancy.
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| Overall design |
The cohort has material from 2 AT/RT patients, 3 MB patients and 5 Coroid plexus tumor (PLEX) patients. It consists of 10 RNA-seq samples and 10 RRBS samples from the same tumours, but due to ethical reasons, the raw material cannot be published. Processed files (Gene counts and the methylation percentages in regional level (1000bp regions) are provided.
Additionally, CUT&RUN data from 4 cell lines (3 AT/RT, 1 MB) with two technical replicates each. The processed MACS3 peaks are provided.
CUT&RUN sequencing for NEUROD1 for 3 AT/RT cell lines as well as 1 MB cell lines.
***The submitter declares that Raw data cannot be published due to ethical reasons***
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| Web link |
https://www.life-science-alliance.org/content/7/6/e202302088
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| Contributor(s) |
Pekkarinen M, Nordfors K, Uusi-Mäkelä J, Kytölä V, Hartewig A, Huhtala L, Rauhala M, Urhonen H, Häyrynen S, Afyounian E, Yli-Harja O, Zhang W, Helen P, Lohi O, Haapasalo H, Haapasalo J, Nykter M, Kesseli J, Rautajoki KJ |
| Citation(s) |
38499326 |
| Submission date |
Feb 28, 2022 |
| Last update date |
Mar 22, 2024 |
| Contact name |
Kirsi Rautajoki |
| E-mail(s) |
kirsi.rautajoki@tuni.fi
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| Organization name |
Tampere university
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| Street address |
Arvo Ylpön katu 34
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| City |
Tampere |
| ZIP/Postal code |
33520 |
| Country |
Finland |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (31)
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| GSM5920698 |
20_DNA, M2 |
| GSM5920699 |
15_DNA, M3 |
| GSM5920700 |
1_DNA, P1 |
| GSM5920701 |
2_DNA, P2 |
| GSM5920702 |
16_DNA, P3 |
| GSM5920703 |
5_DNA, P4 |
| GSM5920704 |
21_DNA, P5 |
| GSM5920705 |
A1 |
| GSM5920706 |
A2 |
| GSM5920707 |
M1 |
| GSM5920708 |
M2 |
| GSM5920709 |
M3 |
| GSM5920710 |
P1 |
| GSM5920711 |
P2 |
| GSM5920712 |
P3 |
| GSM5920713 |
P4 |
| GSM5920714 |
P5 |
| GSM8065048 |
CRL-3020, rep A, NEUROD1 (CUT&RUN) |
| GSM8065049 |
CRL-3020, rep B, NEUROD1 (CUT&RUN) |
| GSM8065050 |
CRL-3036, rep A, NEUROD1 (CUT&RUN) |
| GSM8065051 |
CRL-3036, rep B, NEUROD1 (CUT&RUN) |
| GSM8065052 |
CRL-3038, rep A, NEUROD1 (CUT&RUN) |
| GSM8065053 |
CRL-3038, rep B, NEUROD1 (CUT&RUN) |
| GSM8065054 |
CRL-3021, rep A, NEUROD1 (CUT&RUN) |
| GSM8065055 |
CRL-3021, rep B, NEUROD1 (CUT&RUN) |
| GSM8065056 |
CRL-3021, positive control |
| GSM8065057 |
CRL-3021, negative control |
| GSM8065058 |
CRL-3038, positive control |
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| Relations |
| BioProject |
PRJNA810995 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE197569_RAW.tar |
2.6 Mb |
(http)(custom) |
TAR (of NARROWPEAK) |
| GSE197569_methylation_matrix_with_window_size_1000_read.thr10.txt.gz |
18.2 Mb |
(ftp)(http) |
TXT |
| GSE197569_transcript_level_raw_counts_kallisto.txt.gz |
4.8 Mb |
(ftp)(http) |
TXT |
| Raw data not provided for this record |
| Processed data are available on Series record |
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