Scientists have identified a new mechanism by which so-called “jumping genes”—mobile DNA elements known as retrotransposons—can contribute to the development of cancer.

These elements, some of which belong to the LINE-1 family, were traditionally thought to act only by copying themselves and inserting those copies into different regions of the genome, occasionally causing mutations.

However, new work published in Cancer Discovery shows that their influence is broader and more complex.

LINE-1 is one of the most abundant retrotransposons in the human genome. In normal cells it is tightly suppressed, but in cancer cells it is often reactivated. The researchers developed a specialized method to analyze chromatin structure—the three-dimensional organization of DNA—which allowed them to study how activated LINE-1 elements interact with their surrounding chromatin environment.

The scientists found that RNA produced by certain evolutionarily “young” LINE-1 elements remains associated with chromatin and actively reshapes the genome’s three-dimensional structure. These changes bring together regions of DNA that are normally far apart, creating new physical “contacts.” As a result, genes that promote rapid growth and division of cancer cells become activated.

The team termed these active structural hubs HILLs (highly interactive LINE-1 loci). These loci act like “stitches,” linking distant parts of chromatin and creating an environment that favors the expression of oncogenes—genes that drive tumor growth.

Importantly, the role of LINE-1 in cancer is not limited to the introduction of mutations. According to the researchers, the primary mechanism involves alterations in the three-dimensional architecture of the genome, leading to stronger and more sustained activation of cancer-related genes than in normal cells. Nearly all cancer samples examined showed LINE-1 activation and the formation of HILL structures.

The authors believe this discovery could change how the role of “jumping genes” in oncology is understood and help explain why cancer progresses more rapidly or becomes more resistant to therapy in some patients. In the future, they suggest, these insights could lead to new diagnostic and therapeutic approaches aimed at regulating the spatial organization of the genome.