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

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.