NIH R01 · 2024
MECHANISMS OF POL II ELONGATION IN DIFFUSE MIDLINE GLIOMA
Project Summary/Abstract Diffuse midline gliomas (DMGs) are aggressive brain tumors in both children and adults with no effective therapies. Over 80% of pediatric DMG and a majority of adult DMG harbor non-synonymous mutations in histone H3 (H3.3K27M and H3.1K27M), which dysregulate chromatin and result in aberrant Pol II transcription in brain tumors compared to normal tissue. Aberrant transcription is not only a cause of tumorigenesis, but also a druggable vulnerability as there are multiple studies investigating the utility of Pol II and epigenome-targeting drugs for the treatment of cancer. Despite the initial promise of compounds targeting transcriptional dysregulation as potential…
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