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PETBioNewsNewsTumour cells alter 3D structure of DNA to boost activity of oncogenes

BioNews

Tumour cells alter 3D structure of DNA to boost activity of oncogenes

Published 14 May 2021 posted in News and appears in BioNews 1095

Author

Tsvetana Stoilova

PET BioNews

Using a new algorithmic approach, scientists have found that cancer cells can hijack the normal chromosome structure to increase the activity of cancer-promoting genes...

Using a new algorithmic approach, scientists have found that cancer cells can hijack the normal chromosome structure to increase the activity of cancer-promoting genes. 

Tumour cells can differ from normal cells in many different ways, but all these differences are rooted in changes to the DNA of the cell's genome. Researchers in Switzerland have been focusing on the DNA organisation within chromosomes to understand how cells modify the expression of oncogenes – genes known to promote tumour growth – and have designed an algorithm called Calder to track how epigenetic changes can influence the interactions of different genomic regions.

'We used Calder to compare the spatial organisation of the genome in more than a hundred samples. But this organisation is not static and, just like Alexander Calder's mobile sculptures, it can rearrange its pieces,' said Professor Giovanni Ciriello, who led the team at the University of Lausanne.

Using the same algorithm, a team led by Professor Elisa Oricchio, from the École Polytechnique Fédérale de Lausanne in Switzerland, studied the 3D DNA structure in normal and B-cell lymphoma tumour cells. They found that in cancer cells spatial reorganisation of the genome occurs due to epigenetic changes, which ultimately leads to new gene interactions and increased activity of oncogenes. 

They also discovered that parts of different chromosomes can swap, assuming a new 3D structure, which changes epigenetic signatures and thus promote oncogenes, driving cell expansion. 

'Considering the spatial organisation of DNA in the nucleus provides a new lens to understand how tumour cells originate, and how therapeutic modulation of epigenetic marks can block tumour progression,' said Professor Oricchio.

The research was published in Nature Communications and Nature Genetics.

Sources and References

  • 10/05/2021
    Nature Genetics
    Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci
  • 10/05/2021
    Nature Communications
    Systematic inference and comparison of multi-scale chromatin sub-compartments connects spatial organization to cell phenotypes
  • 11/05/2021
    École polytechnique fédérale de Lausanne
    Cancer cells hijack the 3D structure of DNA
  • 11/05/2021
    AZO Life Sciences
    Cancer cells re-organise DNA structure to ramp up the activity of oncogenes

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Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the output from a DNA sequencing machine.
CC BY 4.0
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