How genome doubling helps cancer develop

Prof. Oricchio’s group at EPFL and Prof. Ciriello’s group at UNIL have uncovered a new way in which cancer can develop: whole genome doubling (WGD) changes the way DNA is organized in the 3D space, leading to the activation of oncogenes that drive cancer growth.

Chromosomes in cells with whole genome doubling.
Credit: Elisa Oricchio/Giovanni Ciriello (EPFL/UNIL)

In a study published in Nature, the scientists show that whole genome doubling (WGD) can affect the 3D organization of the chromatin inside the cell through a phenomenon called “loss of chromatin segregation”.

The researchers looked at cells that lack the tumor suppressor gene p53, making them prone to WGD. They found that WGD leads to a reduction in the segregation of chromatin’s structural elements, such as loops, domains, and compartments, upending its careful organization in the cell. The result is a mixing of genetic material that is normally kept separate, changing the position of genomic regions in the 3D space, known as “sub-compartment repositioning” – setting the stage for the activation of oncogenes.

The work provides a new way of looking at the role of WGD and chromatin organization in the development of cancer. In the future, highly multiplexed single-cell molecular profiles, combined with barcoding technologies and new computational approaches, could help to further uncover what role disorganization of chromatin’s 3D structure plays in transforming a cell into a cancerous one.

Congratulations to both teams !


Ruxandra A. Lambuta, Luca Nanni, Yuanlong Liu, Juan Diaz-Miyar, Arvind Iyer, Daniele Tavernari, Natalya Katanayeva, Giovanni Ciriello, Elisa Oricchio. Whole genome doubling drives oncogenic loss of chromatin segregation. Nature 15 March 2023. DOI: 10.1038/s41586-023-05794-2