Dual-label optical genome mapping for the identification of novel co-occurring genetic and epigenetic alterations in diffuse midline gliomas

Dr. Miriam Bornhorst – Children's National Health System Department of Neurology, Washington D.C.

We have learned a tremendous amount of information about how specific genomic (within the gene itself) and epigenetic (external triggers that turn genes “on” or “off”) changes within pediatric brain tumors drive growth. Despite this knowledge, current testing methods are not always able to detect all the genomic findings in tumors. This is particularly true for structural variants (SVs) and whole DNA epigenetic patterns. Dual-Label Optical Genome Mapping (DL-OGM) is a new method specifically designed to effectively detect both SV and methylation (epigenetic) changes on single, long strands of DNA. This study will be the first to use DL-OGM for discovering tumor-specific genetic and epigenetic changes in diffuse midline gliomas (DMGs). Results from this study will impact management of patients with DMGs in three ways: First, DL-OGM allows for separation of tumor cell populations based on epigenetic patterns and SV populations, which will provide a novel assessment of differences between the same type of tumors in multiple patients. Second, this study will provide extensive SV and whole genome methylation datasets which can be incorporated, along with sequencing data, into diagnostic algorithms. Finally, novel recurring SVs can be explored as targets for molecular therapies, expanding treatment options for children with DMGs. Once established, these methods/techniques could be applied to other brain tumors or cancer types.