Researchers Discover Cancers of Epigenetic Origin without DNA Mutation

A research team including scientists from the Institut de Génétique Humaine at Université de Montpellier and the Centre National de la Recherche Scientifique (CNRS), the largest French public scientific research organization, has discovered that cancer can be caused entirely by epigenetic changes,¹ in other words, changes that contribute to how gene expression is regulated.

Published in Nature, the findings explain in part why, despite an identical genome, an individual can go on to develop differently.

While studies have already described the influence of epigenetic processes in the development of cancer, this may be the first time that scientists have demonstrated that genetic mutations are not essential for the onset of the disease.

The discovery prompts scientists to reconsider what has been known about cancer for more than 30 years, where researchers assumed that cancers are predominantly genetic diseases caused necessarily by DNA mutations that accumulate at the level of the genome.²

To demonstrate this, the research team focused on epigenetic factors that can alter gene activity. By causing epigenetic dysregulation³ in Drosophila, and then restoring the cells to their normal state, scientists have found that part of the genome remains dysfunctional. This phenomenon induces a tumor state that is maintained autonomously and continues to progress, keeping in memory the cancerous status of these cells even though the signal that caused it has been restored.

Published on April 24, 2024, in the journal Nature, their paper titled, Transient loss of Polycomb components induces an epigenetic cancer fate, hopes to open up new therapeutic avenues in oncology.

Further information:

Epigenetics is the study of the mechanisms that facilitate the inheritance of different gene expression profiles in the presence of the same DNA sequence.
The genome is defined as the set of genetic material—and therefore the entire DNA sequence—contained in a cell or organism.
Scientists focused on epigenetic factors called Polycomb proteins, which regulate the expression of key genes, and are dysregulated in many human cancers. When these proteins are experimentally removed, the activity of the targeted genes is disrupted: some can activate their own transcription and self-maintain. When Polycomb proteins are integrated back into the cell, a subset of the genes are resistant to the proteins and remain dysregulated through cell division, allowing the cancer to continue to progress.