An international team of researchers led by Dr Ari Melnick , Director of the Josep Carreras Leukaemia Research Institute (Spain) and Dr Darko Barisic, from Weill Cornell Medicine (United States), has discovered how certain genetic mutations alter the 3D organisation of DNA inside cells, changing the activity of genes in ways that can favour the development of B-cell lymphomas, a group of cancers affecting the B lymphocytes, a type of immune cell.
The study, published in Nature , focuses on a group of proteins known as the BAF complex, which helps control gene activity. Mutations affecting this complex are found in many types of cancer, including B-cell lymphomas, but scientists have not fully understood how these alterations contribute to cancer development.
The international research team found that when the function of a particular form of the BAF complex is disrupted, another protein, called CTCF, can interact to regions of DNA that it couldn’t reach it before. This interaction changes how DNA is folded and organised inside the cell nucleus, altering gene activity and promoting cell proliferation, which can contribute to the development of B-cell lymphomas.
These findings provide new insights into how mutations affecting BAF can contribute to lymphoma development. Although the research focused primarily on B-cell lymphomas, the team observed similar changes in other cell types, suggesting that the mechanism may also be relevant to other cancers.
How the organisation of DNA influences cancer development
DNA contains the genetic instructions that cells need to function. However, these instructions are not simply arranged in a straight line. Inside the nucleus, DNA is folded into a complex three-dimensional structure that helps determine which genes are active and how they are regulated.
The BAF complex plays an important role in this process by controlling access to different regions of DNA. When its function is disrupted by certain mutations, the normal regulation of gene activity can be altered.
In the study, researchers found that the loss of function of a particular form of BAF, known as cBAF, allowed CTCF, a protein involved in organising DNA, to bind to regions that would normally be less accessible.
This increased binding changed the way DNA was folded, disrupting some of the interactions that normally regulate gene activity. In the experimental models, these changes were associated with increased cell proliferation, a process that can contribute to cancer development.
An unexpected discovery
BAF is generally known for making DNA more accessible. But here, the researchers found that disrupting its function had an unexpected effect at sites recognised by CTCF , making these regions more accessible rather than less.
"These findings were unexpected, as they reveal a paradigm for how control of genes is coordinated and balanced by the various types of BAF complexes through tight control of 3D organization of the genome," says Dr Ari Melnick , co-corresponding author and Director of the Josep Carreras Institute
Potential targets for future lymphoma treatments
The team also investigated whether interfering with the proteins involved in this process could reverse some of the effects caused by the loss of BAF function.
In experimental models, the researchers found that disrupting CTCF or another related protein complex could reverse changes associated with the loss of cBAF function. They also found an association between certain alterations affecting CTCF and better patient outcomes.
These results suggest that CTCF and proteins that work alongside it could represent potential targets for future treatments against B-cell lymphomas carrying these mutations.
However, the findings are still at an experimental stage. Further research will be needed to establish whether targeting this mechanism could lead to effective therapies.
"Importantly, these findings help us establish a unifying mechanism for one of the most common classes of cancer mutations and identify CTCF and its partner proteins as candidate therapeutic targets in these cancers," explains Dr Darko Barisic , from Weill Cornell Medicine.
The study was jointly supervised by Dr Melnick and Dr Barisic, with Dr Cem Meydan, also from Weill Cornell Medicine, as a co-corresponding author. The first authors were Dr Sonia Debek, Dr Cem Meydan and Dr Christopher R. Chin.
Researchers from Memorial Sloan Kettering Cancer Center and The Rockefeller University, both in the United States, also contributed to the study.
Reference article: Debek, S., Meydan, C., Chin, C. R. et al. SWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin . Nature (2026). https://doi.org/10.1038/s41586-026-11197-w
About the Josep Carreras Leukaemia Research Institute
The Josep Carreras Leukaemia Research Institute is Spain's dedicated research institute for blood cancers, one of the very few free-standing institutes in the world focused exclusively on this disease space.
Founded in 2010, the Institute was recognized in 2024 as a Severo Ochoa Centre of Excellence by the Spanish Ministry of Science, Innovation and Universities. IJC is also a centre of excellence CERCA of the Catalan Government and is embedded in a network of six affiliated hospitals across Catalonia. The Institute’s researchers bring together expertise in epigenetics, immunology, stem cell biology, spatial transcriptomics, computational oncology, and clinical investigation, all directed at a single purpose: curing blood cancers.
The Institute's translational strategy is built around three interconnected pillars: the Catalonia Translational Working Groups, which unite clinicians, scientists, and diagnostics experts around the most urgent cross-disease challenges in hematological malignancy; PATH2CURE, a comprehensive therapeutics platform that advances discoveries from target identification through preclinical validation toward clinical application; and the Center for 22nd Century Diagnostics (C22D), a joint initiative with the Barcelona Supercomputing Center that integrates spatial biology, multi-omics, and artificial intelligence to generate dynamic, patient-specific diagnostic models capable of predicting how disease will evolve and resist. Together, these pillars form a continuous translational cycle connecting patient care, biological discovery, and clinical innovation. This is made possible thanks to the philanthropic mission of the Josep Carreras Leukaemia Foundation and by the commitment of every person at the Institute to the patients who cannot afford to wait.
Nature
Experimental study
Cells
SWI/SNF complexes shape 3D chromatin architecture through CTCF and cohesin