The BAF complex is responsible for mediating DNA packaging and can inhibit tumor development in a variety of tissue types. Researchers at the Stanford University School of Medicine found through proteomics and bioinformatics that the BAF complex is mutated in about one-fifth of human cancers, indicating that the complex plays an important role in the development of malignant tumors. In addition, the researchers believe that the complex may have many other functions besides regulating chromatin. "Although we know that the BAF complex has a cancer-suppressing effect, we did not realize that its impact was so widespread before," said Dr. Cigall Kadoch, co-first author of the article. The research was published in the journal Nature Genetics on May 5. Dr. Cigall Kadoch and Dr. Diana Hargreaves were the co-first authors of the article, and Professor Gerald Crabtree was the senior author of the article. BAF is a chromatin regulatory complex. These proteins tightly compress DNA while allowing DNA replication and gene expression. Crabtree Laboratories has been working on BAF complex and its function for many years. In 2011, they published a study in Nature magazine that affected subunits in the BAF complex through miRNA, turning human fibroblasts into neurons. "The chromatin regulatory complex compresses long DNA in the nucleus," Crabtree said. "But it does not affect the replication of DNA and its selective expression in different tissues. We discovered in 1994 that the BAF complex can inhibit tumors. Now we see that in nearly 20% of human malignant tumors, this complex Mutations have occurred. "Studies have shown that mutations in specific subunits (or specific subunit combinations) in the BAF complex can predict the development of corresponding cancers. And in some cases, a mutation in a single subunit is enough to drive cancer development. "For example, we discovered the new subunit SS18," Kadoch said. "This subunit encodes a chromosomal translocation mutation in the gene and is a hallmark of synovial sarcoma." Kadoch and Crabtree published a study in Cell magazine in March and revealed The role of BAF complex in synovial sarcoma. The composition of the BAF complex differs between different types of cells. Kadoch uses an antibody that recognizes the core components of BAF to purify the complete BAF complex in a variety of cell types, including embryonic stem cells, skin cells, and nerve cells. She then analyzed the isolated protein and found that mutations in the BAF complex are very common. Kadoch identified 7 new BAF protein components through the above method. She and Hargreaves then reviewed 44 tumor-wide genome sequencing studies involving mutations in the BAF complex. The researchers combined these research data with their own experiments and came up with a surprising finding: 19.6% of human tumors have at least one mutation in the BAF complex. In addition, some cancers (such as synovial sarcoma) are caused by a mutation in a single subunit of BAF. This study shows that the BAF complex has an important protective role in the development of many different cancers. At present, researchers are studying in depth, trying to analyze the mechanism of related mutations affecting the tumor suppressive effect of BAF complex.
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