Changes in a group of genes called BAF may help cancer cells grow by altering how DNA is folded and which genes are switched on. As reported by SciTechDaily, a new study from Weill Cornell Medicine describes a possible link between these mutations and a protein called CTCF. In experiments, removing CTCF reversed some cancer-promoting effects in an animal model.
The findings, published in Nature, may help researchers understand why BAF mutations appear in many cancer types. They also point to possible targets for future treatments—but no therapy based on this research has yet been shown to work safely in people.
How DNA organization affects cells
DNA contains the instructions cells use to function. But those instructions are not all active at once. Proteins help package and organize DNA, influencing which genes a cell can access and use.
One of the organizers is the BAF complex, a group of proteins that helps regulate access to DNA. BAF is made up of many parts, and mutations affecting its components have been found in cancers of the breast, ovaries, liver and lymphatic system. Such mutations are estimated to occur in about one-fifth of human cancers.
Researchers have long known that BAF mutations are common in cancer, but how they contribute to tumor growth across different tissues has not been fully clear.
A surprising change in DNA access
The team found that when BAF function was impaired, another protein, CTCF, could attach to many more locations in the DNA. CTCF helps organize DNA into regions and loops, shaping how genes connect with the controls that regulate them.
The result challenged what researchers expected. As Dr. Meydan explained, scientists thought losing BAF would make DNA less accessible. Instead, it made more sites available to CTCF.
Using cell and animal models with impaired BAF function, the researchers observed increased CTCF binding at thousands of locations across the genome. This appeared to alter DNA folding and disrupt normal relationships between genes and their regulatory regions. The changes in gene activity were associated with faster cell division.
The researchers also examined data from people with cancer. Their analysis supported a role for CTCF in the process, although patient data alone cannot show that CTCF changes caused differences in outcomes. In animal experiments, removing CTCF reversed some effects of BAF mutations, providing stronger evidence that CTCF contributes to the process in those models.
Other possible targets—and important unknowns
The team also identified two protein complexes, PBAF and ISWI, that appeared to work with CTCF in driving the DNA changes. Removing either complex also blocked some effects of BAF mutations in experimental models.
“This helps us establish a unifying mechanism” for a widespread class of cancer mutations, said co-corresponding author Dr. Darko Barisic. He and his colleagues view CTCF and its partner proteins as potential targets for future research.
That does not mean these proteins can already be safely blocked as a cancer treatment. They also have important roles in normal cells. Researchers must determine how the changes affect the genome, whether a drug can interfere with the process, and whether doing so would be safe and effective in people.
For now, the work offers a possible explanation for how BAF mutations may promote cancer and a direction for further study—not a new treatment option for patients.
