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Full-Text Articles in Medical Sciences
Genomic Instability And The Oncohistone H3k27m Drive Gliomagenesis In A Murine Model, Lee J. Pribyl
Genomic Instability And The Oncohistone H3k27m Drive Gliomagenesis In A Murine Model, Lee J. Pribyl
Theses and Dissertations (ETD)
Maintaining genome stability is crucial for human health and it is of particular importance in neural cells during early brain development. Genome maintenance occurs at two broad stages; surveillance during DNA replication and DNA damage repair in differentiating and mature cells. Neural cells are particularly sensitive to DNA strand breaks and defective DNA damage responses can result in detrimental effects on the nervous system, including cancer. Multiple DNA repair pathways play critical roles in preventing DNA damage accumulation in stem and neural progenitor cells. The mechanisms that protect progenitor genomes also suppress DNA mutations that can result in cancer. A …
Novel Oncogenic Drivers In Pediatric Gliomagenesis, Alexander K. Diaz
Novel Oncogenic Drivers In Pediatric Gliomagenesis, Alexander K. Diaz
Theses and Dissertations (ETD)
Pediatric high-grade gliomas (pHGGs), with a two-year survival rate of less than 20%, are some of the most aggressive human cancers. This dissertation begins with our analysis of 127 pHGGs, including brainstem (BS) and non-brainstem (NBS) tumors, from 118 patients using next-generation sequencing technologies. Nearly one-third of BS-HGGs, also known as diffuse intrinsic pontine gliomas (DIPGs), harbored somatic heterozygous missense mutations in ACVR1, coding for a receptor serine-threonine kinase involved in bone morphogenetic protein (BMP) signaling. These alterations led to gain-of-function as evidenced by increased phosphorylation of downstream targets in primary astrocytes and zebrafish embryo ventralization. Whole-genome sequencing and …