A new study from Weill Cornell Medicine suggests that the way DNA folds inside brain cells could play a key role in the development of glioblastoma, one of the most aggressive and deadly types of brain cancer.
The research, published in Molecular Cell, offers a fresh way to think about cancer—not just by looking at gene mutations, but by understanding how genes interact in three-dimensional space.
Normally, our DNA stretches about six feet long, but it has to fit inside a cell nucleus that’s smaller than a grain of sand.
To manage this, DNA folds and loops tightly, bringing distant regions together.
Dr. Effie Apostolou, who co-led the study, explained that by studying the 3D structure of DNA, the team found hubs where different parts of the genome gather and work together, even if they’re far apart on the DNA strand.
In healthy cells, these hubs help coordinate important biological processes, like development.
But when researchers looked at glioblastoma tumor cells, they found something troubling: cancer-causing genes were clustering together with other genes that weren’t previously linked to brain cancer, creating powerful networks that seemed to drive the disease.
Dr. Howard Fine, who co-led the study, said that these 3D hubs may be just as important—or even more important—than traditional gene mutations in fueling cancer growth.
To test this idea, the team used CRISPR interference, a gene-editing tool, to shut down a suspected cancer-related hub in glioblastoma cells from patient tumor samples.
When they silenced the hub, many cancer-related genes became less active, and the cancer cells lost their ability to grow into tumor-like structures in the lab.
Encouraged by these results, the researchers looked at other types of cancer and found similar 3D hubs in tumors like melanoma, lung, prostate, and uterine cancers. Each type of cancer had its own set of hubs, but some hubs appeared across multiple cancers.
Interestingly, these hubs usually weren’t caused by obvious mutations like broken DNA. Instead, they often formed due to epigenetic changes—alterations in how DNA is packaged and controlled without changing the actual DNA sequence.
Proteins that bind to DNA and regulate gene activity appear to help create and maintain these hubs.
The discovery of these 3D control centers opens up new possibilities for cancer treatment. Instead of only targeting broken genes, future therapies might aim to disrupt these hubs and prevent cancer cells from coordinating their growth.
Dr. Fine said the next steps will be to learn how these hubs form and figure out safe ways to interfere with them, offering hope for better ways to fight brain cancer and other aggressive tumors.
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