Aditi Kaveti ‘23

Human bodies rely on tumor suppressors to regulate cell production. The bromodomain-containing protein 9 (BRD9) RNA molecule is an important tumor suppressor for many types of cancer, including uveal melanoma, chronic lymphocytic leukemia, and pancreatic cancer. BRD9 is extremely important because it represses abnormal cell reproduction and the formation of tumors. A mutation in the gene that produces the BRD9 RNA molecule will lead to an incoherent genetic message due to the previously altered DNA. Researchers are still trying to understand how these mutations affect certain processes, as well as how to prevent or change their outcomes. Dr. Robert Bradley at the Fred Hutchinson Cancer Research Center and Dr. Omar Abdel-Wahab at the Memorial Sloan Kettering Cancer Center found that a single mutation in the SF3B1 gene caused many cancers. 

Bradley and Abdel-Wahab analyzed RNA sequencing data from a series of patients and found that the SF3B1 mutation would produce an abnormal form of the BRD9 RNA molecule. Once the researchers identified the mutation in the gene, they used genome engineering, computing power, and sequencing technology to investigate ways to block tumor progression. Researchers monitored gene expression and performed sequencing tests to determine specific treatments that slowed tumor growth.

The research has not yet been tested in humans, but Bradley and Abdel-Wahab determined that potential targeted therapeutics could slow down or prevent a patient’s tumor growth by modifying the mutated BRD9 RNA molecule in their cells. The SF3B1 gene is the most frequently mutated splicing factor gene and causes cancer cells to produce an abnormal form of the BRD9 RNA molecule. The researchers explained that it is extremely important, as it allows clinicians to evaluate where and how the cancer can be targeted. The researchers need to develop this study beyond an assumption based on principle, and they hope to eventually test their theory with clinical therapy. 

References:

1. R. Bradley, Spliceosomal disruption of the non-canonical BAF complex in cancer. Nature 574, 432-436 (2019). doi: 10.1038/s41586-019-1646-9
2. Image retrieved from: https://upload.wikimedia.org/wikipedia/commons/3/37/Genetic_code.svg