Characterizing therapeutic vulnerabilities in mismatch repair deficient pediatric high-grade gliomas
Mentor Name: Rameen Beoukhim
Pediatric high-grade gliomas are among the most lethal childhood brain tumors. One of the most common treatments is temozolomide, and a common resistance mechanism is loss of mismatch repair. In addition, constitutional mismatch repair (MMR) deficiency syndrome is predisposes children to develop high grade gliomas within their first decade. Discovering synthetic lethalities with MMR deficiency in these tumors therefore has the potential to reveal useful therapeutic targets. The Beroukhim and Bandopadhayay labs have performed genome-wide CRISPR knockout screens and a screen of ~6000 compounds in isogenic glioma cells with and without MMR deficiency, to detect vulnerabilities that are specific to glioma cells that have lost MMR. In my summer project, I will evaluate positive results from these screens across a panel of MMR-proficient and -deficient pediatric high-grade glioma cell lines, to assess whether the screening results reproduce and how generalizable those results are. Ideally this will lead to the identification of possible therapeutic targets in MMR-deficient pediatric high-grade gliomas.
