Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors

Meeri Pekkarinen, Kristiina Nordfors, Joonas Uusi-Mäkelä, Ville Kytölä, View ORCID ProfileMinna Rauhala, Henna Urhonen, Laura Huhtala, Sergei Häyrynen, Ebrahim Afyounian, Olli Yli-Harja, Wei Zhang, Pauli Helen, Olli Lohi, Hannu Haapasalo, Joonas Haapasalo, Matti Nykter, Juha Kesseli, Kirsi J. Rautajoki
doi: https://doi.org/10.1101/2022.03.14.483566
Meeri Pekkarinen
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kristiina Nordfors
2Tampere Center for Child Health Research, Tays Cancer Center, Tampere University and Tampere University Hospital, Tampere, Finland
3Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joonas Uusi-Mäkelä
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ville Kytölä
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minna Rauhala
3Tays Cancer Center, Tampere University Hospital, Tampere, Finland
4Department of Neurosurgery, Tays Cancer Centre, Tampere University Hospital and Tampere University, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Minna Rauhala
Henna Urhonen
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura Huhtala
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sergei Häyrynen
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ebrahim Afyounian
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olli Yli-Harja
5Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
6Institute for Systems Biology, Seattle, WA, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei Zhang
7Cancer Genomics and Precision Oncology, Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pauli Helen
4Department of Neurosurgery, Tays Cancer Centre, Tampere University Hospital and Tampere University, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olli Lohi
2Tampere Center for Child Health Research, Tays Cancer Center, Tampere University and Tampere University Hospital, Tampere, Finland
3Tays Cancer Center, Tampere University Hospital, Tampere, Finland
5Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hannu Haapasalo
5Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
8Fimlab Laboratories ltd., Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joonas Haapasalo
3Tays Cancer Center, Tampere University Hospital, Tampere, Finland
4Department of Neurosurgery, Tays Cancer Centre, Tampere University Hospital and Tampere University, Tampere, Finland
8Fimlab Laboratories ltd., Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matti Nykter
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juha Kesseli
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kirsi J. Rautajoki
1Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
9Tampere Institute for Advanced Study, Tampere University, Tampere, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: kirsi.rautajoki@tuni.fi
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

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. Part of the hypermethylated sites 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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Shifted the focus to atypical teratoid/rhabdoid tumors (AT/RTs). Investigated the contribution of different AT/RT subgroups on our results and found that the detected methylation patterns were largely shared between AT/RT subgroups. Unified the criteria for differential DNA methylation used for TF-enrichment and gene expression correlation analysis. Figure 1 updated. Figure 2 revisited. Figure 3 updated. Figure 4 updated. Manuscript text and title updated to reflect these changes. The corresponding author changed her name, which was updated.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted October 01, 2022.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors
Meeri Pekkarinen, Kristiina Nordfors, Joonas Uusi-Mäkelä, Ville Kytölä, Minna Rauhala, Henna Urhonen, Laura Huhtala, Sergei Häyrynen, Ebrahim Afyounian, Olli Yli-Harja, Wei Zhang, Pauli Helen, Olli Lohi, Hannu Haapasalo, Joonas Haapasalo, Matti Nykter, Juha Kesseli, Kirsi J. Rautajoki
bioRxiv 2022.03.14.483566; doi: https://doi.org/10.1101/2022.03.14.483566
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors
Meeri Pekkarinen, Kristiina Nordfors, Joonas Uusi-Mäkelä, Ville Kytölä, Minna Rauhala, Henna Urhonen, Laura Huhtala, Sergei Häyrynen, Ebrahim Afyounian, Olli Yli-Harja, Wei Zhang, Pauli Helen, Olli Lohi, Hannu Haapasalo, Joonas Haapasalo, Matti Nykter, Juha Kesseli, Kirsi J. Rautajoki
bioRxiv 2022.03.14.483566; doi: https://doi.org/10.1101/2022.03.14.483566

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cancer Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4246)
  • Biochemistry (9175)
  • Bioengineering (6807)
  • Bioinformatics (24066)
  • Biophysics (12160)
  • Cancer Biology (9567)
  • Cell Biology (13847)
  • Clinical Trials (138)
  • Developmental Biology (7661)
  • Ecology (11739)
  • Epidemiology (2066)
  • Evolutionary Biology (15547)
  • Genetics (10673)
  • Genomics (14365)
  • Immunology (9515)
  • Microbiology (22916)
  • Molecular Biology (9135)
  • Neuroscience (49170)
  • Paleontology (358)
  • Pathology (1487)
  • Pharmacology and Toxicology (2584)
  • Physiology (3851)
  • Plant Biology (8351)
  • Scientific Communication and Education (1473)
  • Synthetic Biology (2301)
  • Systems Biology (6207)
  • Zoology (1304)