Brent Orr Lab

The research in our laboratory focuses on the molecular classification of brain tumors. We conduct our work with a two-armed approach that defines the molecular substructure of different entities and implements those findings in the clinical setting.

Some of our efforts have used methylation profiling to clarify and update the tumors included in the WHO Classification of Tumours of the Central Nervous System (CNS). A portion of our earliest endeavors focused on gliomatosis cerebri and primitive neuroectodermal tumors, the latter of which led to the identification of four novel brain tumor entities that are now included in the WHO classification guide.

Our research also extends into the molecular subgroup classification of other solid tumors and sarcomas, including adrenocortical tumors, rhabdomyosarcoma, and gliomas. Our lab’s recent discovery shows radiation-induced gliomas generally fall into a single molecular group and have specific copy-number driver abnormalities.

Once we identify the molecular subgroups of tumors, we use that information in novel applications. For example, we implemented DNA methylation profiling as a supervised classification model in the clinical lab, and our novel machine-learning approach now serves as a clinical test to stratify patients on clinical trials. We are currently exploring novel ways to conduct risk stratification and grading within molecular groups or predict molecular tumor classes from histology images.

Of note, our lab is a pathology lead on the COMET (Solid Tumor COmprehensive METhylation Database) program at St. Jude. COMET is a Blue Sky initiative that focuses on the development of a pediatric solid tumor database of DNA methylation data. The goal is to understand the molecular substructure of non-brain solid tumors and then incorporate those into our diagnostic models. We have gathered more than 5,000 samples over a two-year period, and the project will serve as the foundation for a variety of other research projects at St. Jude.

Through innovative efforts like COMET and our laboratory’s work to enhance the understanding of brain and solid tumors at the molecular level, we contribute to the advancement of cures for children with catastrophic disease.