We are requesting 12 flash frozen specimens, along with 2 suspended cell pellets. Our experiments require at least 100mg of tissue for each frozen specimen, and we have identified representative specimens that we will not exhaust. Experiments will be performed in triplicates and with at least 2 biological repeats. In Aim 1, using frozen tissue, we will compare expression of senescence biomarkers in glioma tissue samples and correlate prevalence of senescent markers with glioma aggressiveness. In Aim 2, using the cell lines, we will analyze the effects of manipulations of RTK fusions on senescence and tumorigenesis in primary human gliocytes and cell lines derived from iHGG and pHGG tissues.
What are the goals of this project?
The goals of the project are to compare expression of senescence biomarkers in glioma tissue samples and correlate prevalence of senescent markers with glioma aggressiveness as well as to analyze the effects of manipulations of RTK fusions on senescence and tumorigenesis in primary human gliocytes and cell lines derived from iHGG tissues.
What is the impact of this project?
It is expected that the percentage of cells positive for the senescence markers in RTK-fused iHGG will be similar to MAPK-activated pLGG, and higher compared to pediatric/adult HGG specimens. These results will suggest that senescence contributes to the different behaviors and outcomes of infant and pediatric/adult glioma. The mechanism responsible for this difference in senescence induction between infant, pediatric, and adult glioma cells by comparing the ability of the RTK-fusions to induce senescence in gliocytes or brain tumor cells from infants and older children or adults will be further investigated.
Why is the CBTN request important to this project?
CBTN provides a large cohort of samples from children and young adults with brain tumors. Tissue from the CBTN will provide the needed specimens to increase the number of samples in each infant/pediatric group, namely the iHGG, pLGG, and pHGG groups. In addition, the iHGG cell lines derived from patients without RTK fusions will provide with a tool for analyzing the effect of RTK fusion protein overexpression on senescence and tumorigenesis.
CBTN will be contributing to this project by providing 12 flash frozen tissue samples and 2 suspended cell pellets.
David Kram, MD, MCR
David Kram is a pediatric neuro-oncologist and Medical Director of the Pediatric Brain Tumor Program at Wake Forest School of Medicine/Brenner Children’s Hospital. David’s research focuses on infant and pediatric glioma behavior, invasiveness, and response to therapy. He is committed to finding bett
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