Good news! Cancer is history (soon)!
"Gliomas are the most common brain tumors, and many start off growing slowly as “low-grade” tumors before inevitably becoming aggressive, lethal, and “high grade.” New research offers an explanation for this deadly transformation. ...
The team found that over time, these initially slow-growing tumors acquire new, cancer-driving mutations that send them into overdrive. The scientists also observed that the composition of cells in the tumor changes, further shifting the gliomas into a fast-growth mode. ...
Their analysis also revealed a shift in the identity of the tumor cells. Most cells in the early-stage tumors resembled those that specialize in generating glia. Later-stage tumors, however, were dominated by cancer cells that look like more primitive neural progenitor cells (NPCs). ...
Moreover, the researchers discovered a new effect of the excessive methylation. They determined that this epigenetic change represses the immune system’s tumor-fighting interferon response, and suggest that treatment with a methylation-reducing compound may restore it. ..."
From the abstract:
"Isocitrate dehydrogenase (IDH) mutants define a class of gliomas that are initially slow-growing but inevitably progress to fatal disease. To characterize their malignant cell hierarchy, we profiled chromatin accessibility and gene expression across single cells from low-grade and high-grade IDH-mutant gliomas and ascertained their developmental states through a comparison to normal brain cells. We provide evidence that these tumors are initially fueled by slow-cycling oligodendrocyte progenitor cell-like cells. During progression, a more proliferative neural progenitor cell-like population expands, potentially through partial reprogramming of ‘permissive’ chromatin in progenitors. This transition is accompanied by a switch from methylation-based drivers to genetic ones. In low-grade IDH-mutant tumors or organoids, DNA hypermethylation appears to suppress interferon (IFN) signaling, which is induced by IDH or DNA methyltransferase 1 inhibitors. High-grade tumors frequently lose this hypermethylation and instead acquire genetic alterations that disrupt IFN and other tumor-suppressive programs. Our findings explain how these slow-growing tumors may progress to lethal malignancies and have implications for therapies that target their epigenetic underpinnings."
Evolving cell states and oncogenic drivers during the progression of IDH-mutant gliomas (no public access)
Glioma tumor cells seen under a microscope
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