Mount Sinai Researchers Discover How Melanoma May Spread to the Brain
Study highlights role of PBAF chromatin remodeling complex in blocking neuronal gene expression
Scientists at the Icahn School of Medicine at Mount Sinai have discovered a possible reason why some cases of melanoma—a dangerous form of skin cancer—spread to the brain. Their study, published in the latest issue of Molecular Cell, highlights the role of a group of proteins called the PBAF chromatin remodeling complex in keeping melanoma from getting worse.
Chromatin is the material that makes up our chromosomes, and it controls how genes are turned on or off. The PBAF complex helps organize this material, acting like a gatekeeper that decides which genes get used. In this study, researchers found that when PBAF is not working properly—which happens in many melanoma tumors—certain neuron-related genes get turned on in skin cancer cells. This may help melanoma survive and grow in the brain.
Brain metastasis occurs when cancer cells from a tumor in another part of the body spread to the brain. It's a common type of brain tumor, often more prevalent than primary brain tumors, which originate in the brain itself. Studies estimate that between 40 percent and 75 percent of people whose melanoma spreads will end up with one or more brain metastases.
“Contrary to common belief of how chromatin remodelers function in gene activation, our research shows that the PBAF complex keeps certain genes shut off in melanoma,” said lead author Emily Bernstein, PhD, Professor of Oncological Sciences, and Dermatology, and Cancer Mechanisms Program Co-leader, Icahn School of Medicine at Mount Sinai. “When this complex is damaged, these genes turn on and may make it easier for the cancer to spread to the brain.”
The team also found that this same pattern of gene activity shows up in melanoma patients with PBAF mutations, especially those whose cancer had already spread to the brain.
“This research could lead to better screening and new treatments that stop melanoma from spreading. Understanding how melanoma spreads to the brain may help doctors monitor high-risk patients more closely,” Dr. Bernstein adds. “The Mount Sinai team will now study how these mutations behave in animal models, especially in brain environments, to learn more about how to stop melanoma from spreading.”
The study was a collaboration with the Herbert Irving Comprehensive Cancer Center at Columbia University, and included important contributions from former Mount Sinai MD/PhD and PhD students Christie B. Nguyen and Saul Carcamo, respectively. It was funded by several major research organizations, including the National Institutes of Health, the Melanoma Research Foundation and the Melanoma Research Alliance.
Read the full manuscript here: https://authors.elsevier.com/c/1kyNh_OylrlzDF
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