3D hotspots of recurrent retroviral insertions reveal long-range interactions with cancer genes
Open accessAbstract
Genomically distal mutations can contribute to the deregulation of cancer genes by engaging in chromatin interactions. To study this, we overlay viral cancer-causing insertions obtained in a murine retroviral insertional mutagenesis screen with genome-wide chromatin conformation capture data. Here we find that insertions tend to cluster in 3D hotspots within the nucleus. The identified hotspots are significantly enriched for known cancer genes, and bear the expected characteristics of bona fide regulatory interactions, such as enrichment for transcription factor-binding sites. In addition, we observe a striking pattern of mutual exclusive integration. This is an indication that insertions in these loci target the same gene, either in their linear genomic vicinity or in their 3D spatial vicinity. Our findings shed new light on the repertoire of targets obtained from insertional mutagenesis screening and underline the importance of considering the genome as a 3D structure when studying effects of genomic perturbations.
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Long-range chromatin interactions have been shown to contribute to oncogenesis caused by retroviral vectors.
“Long-range chromatin interactions have also been shown to contribute to oncogenesis caused by retroviral vectors [55].”
From Clinical use of lentiviral vectors (2018) · cites this paper as [55]
The Discussion reports evidence that long-range chromatin interactions can connect cancer-causing retroviral insertions to target genes in a mouse insertional-mutagenesis screen. For oncogenesis associated with therapeutic retroviral vectors specifically, it says such interactions “might explain” unintended oncogene activation; it does not show that they contribute to that adverse effect. (LLM, conf=0.88)
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Self-citationModelling Crebbp loss in BCL2 driven non-Hodgkin’s lymphoma
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A Genome Model Linking Birth Defects to InfectionsPreprint
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- Authors
- Babaei, S., Akhtar, W., de Jong, J., Reinders, M., & de Ridder, J.
- Affiliations
- Delft University of Technology (NL)
- The Netherlands Cancer Institute (NL)
- Venue
- Nature Communications
- Published
- 2015-02-27
- Volume
- 6
- Issue
- 1
- Pages
- 6381-6381
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4351571
- OpenAlex
- W2029503535
- Cited by
- 37
- References
- 56
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 2 · 2015: 7
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research Repository (Delft University of Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (639.021.233)
- Norwegian Biodiversity Information Centre
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- retroviral integration, 3D genome organization, chromatin looping, cancer genes, insertional mutagenesis, transcription factor binding sites
- MeSH terms
- Animals, Cell Nucleus, Chromatin, Retroviridae Infections, Gene Expression Regulation, Neoplastic, Mutagenesis, Insertional, Virus Integration, Gene Expression Profiling, Mice, Genes, Neoplasm
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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