Harvard Catalyst Profiles

Evidenced by the widespread incorporation of histomolecular entities into the recent WHO classification of CNS tumors, accurate diagnosis and prognostic assessment of brain tumors is heavily reliant on integration with molecular data. Despite advances in the understanding of pathogenic mechanisms leading to gliomagenesis in both adult and pediatric tumors, there remains uncertainty as to how adult tumors with drivers in the MAPK pathway, which are more characteristic of pediatric tumors, present and behave. At BWH, we routinely perform NGS testing of all gliomas seen in practice and have accumulated over 2,000 cases with molecular profiling and detailed clinicopathologic data. Approximately 10% of these tumors show activating genomic alterations in the MAPK pathway, often producing unusual pathology. While current WHO classification relies heavily on methylation cluster analysis to assign diagnoses, we propose using existing comprehensive genomic and transcriptomic profiles to generate diagnostic signatures of existing and novel entities. Furthermore, we have generated many patient-derived models from these tumors, facilitating our ability to test drug sensitivities in vitro and explore novel treatment options. Students interested in joining this project will have the opportunity to collect and organize clinical and pathologic data, as well as analyze multiple modalities of molecular data. Toward this end, some proficiency with bioinformatics, mainly using and optimizing various R packages and generating simple custom scripts for large cohort data analysis is encouraged. Contribution to manuscripts resulting from these efforts will also be expected in exchange for prominent authorship positions.