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

Chromatin accessibility of primary human cancers ties regional mutational processes with tissues of origin

Oliver Ocsenas, Jüri Reimand
doi: https://doi.org/10.1101/2021.05.14.444202
Oliver Ocsenas
1Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada
2Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jüri Reimand
1Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada
2Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
3Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Juri.Reimand@utoronto.ca
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Regional mutagenesis in cancer genomes associates with DNA replication timing (RT) and chromatin accessibility (CA) of normal cells, however human cancer epigenomes remain uncharacterized in this context. Here we model megabase-scale mutation frequencies in 2517 cancer genomes with 773 CA and RT profiles of cancers and normal cells. We find that CA profiles of matching cancers, rather than normal cells, predict regional mutagenesis and mutational signatures, indicating that most passenger mutations follow the epigenetic landscapes of transformed cells. Carcinogen-induced and unannotated signatures show the strongest associations with epigenomes. Associations with normal cells in melanomas, lymphomas and SBS1 signatures suggest earlier occurrence of mutations in cancer evolution. Frequently mutated regions unexplained by CA and RT are enriched in cancer genes and developmental pathways, reflecting contributions of localized mutagenesis and positive selection. These results underline the complex interplay of mutational processes, genome function and evolution in cancer and tissues of origin.

Competing Interest Statement

The authors have declared no competing interest.

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 May 17, 2021.
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.
Chromatin accessibility of primary human cancers ties regional mutational processes with tissues of origin
(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
Chromatin accessibility of primary human cancers ties regional mutational processes with tissues of origin
Oliver Ocsenas, Jüri Reimand
bioRxiv 2021.05.14.444202; doi: https://doi.org/10.1101/2021.05.14.444202
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Chromatin accessibility of primary human cancers ties regional mutational processes with tissues of origin
Oliver Ocsenas, Jüri Reimand
bioRxiv 2021.05.14.444202; doi: https://doi.org/10.1101/2021.05.14.444202

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

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3687)
  • Biochemistry (7782)
  • Bioengineering (5673)
  • Bioinformatics (21259)
  • Biophysics (10566)
  • Cancer Biology (8165)
  • Cell Biology (11920)
  • Clinical Trials (138)
  • Developmental Biology (6748)
  • Ecology (10393)
  • Epidemiology (2065)
  • Evolutionary Biology (13847)
  • Genetics (9700)
  • Genomics (13061)
  • Immunology (8133)
  • Microbiology (19976)
  • Molecular Biology (7841)
  • Neuroscience (43006)
  • Paleontology (318)
  • Pathology (1276)
  • Pharmacology and Toxicology (2257)
  • Physiology (3350)
  • Plant Biology (7219)
  • Scientific Communication and Education (1309)
  • Synthetic Biology (2000)
  • Systems Biology (5529)
  • Zoology (1126)