The slightest genetic mutation can promote the development of cancer. Swiss researchers show that the duplication of genes as well as the disruption of the organization of the chromatin (DNA complex) act together in this direction.
“Whole genome doubling” (WGD) is an event by which all of the chromosomes in a cell are duplicated. Common to about 30% of all human cancers, it promotes genome instability and mutations that contribute to cancer development.
A team of Swiss researchers has shown that, independently, WGD can disrupt the organization of chromatin, the DNA complex that makes up the chromosomes. The specific organization of chromatin allows normal expression of genes, so that the phenomenon of “loss of chromatin segregation” disturbs the positioning of the loops, domains and compartments that constitute it. The normally separated genetic material mixes, the position of the regions of the genome in 3D space is modified and then promotes the activation of oncogenes.
Two independent and complementary mechanisms in the development of cancer
In research published in Nature, the researchers looked at cells that lack the p53 tumor suppressor gene, promoting a genetic disease that causes cancer. They ultimately found that loss of chromatin segregation and chromosomal instability are complementary mechanisms that act together to promote cancer development.
The authors note that the use of single-cell molecular profiles could help to better uncover the role that disorganization of the 3D structure of chromatin plays in the transformation of a cell into a cancerous cell.
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