Genomic Dissection of Structural Mutations Following Telomere Dysfunction in Glioblastoma Cells and Patients
Abstract
Glioblastoma is the most common malignant brain tumor and is considered the deadliest form of human cancer. A normal human cell contains 23 pairs of chromosomes consisting of linear DNA elements that make up one s genome, or genetic code. In cancerous glioblastoma cells, these DNA elements are vastly rearranged, meaning there are additional pieces added, moved from one place to the other, or entirely missing. What causes these widespread genomic rearrangements in glioblastoma cells is not known. At the two ends of each chromosome sits a repetitive DNA sequence called a telomere. Its purpose is to protect chromosome ends from activating DNA repair processes that could damage the integrity of the chromosome. In cancer cells, these telomeres are often short and dysfunctional, which could be a trigger DNA repair to stitch two normally separated chromosomes together. We propose that accidental activation of DNA repair at telomeres is responsible for a large majority of the genomic rearrangements seen in glioblastoma. Dr. Floris Barthel has an outstanding track record investigating genome variation in glioblastoma. His work outlining a DNA-based classification of glioblastoma has influenced the World Health Organization classification of central nervous system tumors. The Virtual Cancer Center Scholar Award provides Dr. Barthel many career development opportunities that will position him as a leader in studies that improve the prevention and therapeutics of glioblastoma. Importantly, the programmed interactions with fellow scholars could lead to life- long collaborations with fellow early career scientists. Defining how dysfunctional telomeres shape the glioblastoma genome will fundamentally change our conceptual understanding of tumor development. In the long run, it will help expose new drug targets and improve treatment options for glioblastoma patients. Glioblastoma is among the top causes of cancer-related deaths in active Service Members and has also been associated with sources linked to military deployment, such as Agent Orange. Funding this proposal therefore stands to benefit all glioblastoma patients and critically, improve the mission readiness of active military personnel.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310844
Entities
People
- Floris Barthel
Organizations
- Translational Genomics Research Institute
- United States Army