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Characterizing Unique Underlying Molecular Features of Spinal Cord Gliomas

Spinal cord gliomas are tumors of the central nervous system that do not yet have clearly defined treatment standards.

Common cancer treatment methods such as extensive resection, radiation and chemotherapy provide limited survival advantage to patients with these tumors.

Frances Chow, MD, a neuro-oncologist at USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC, recently lead a multi-institutional retrospective study to comprehensively characterize spinal cord gliomas.

The study’s results, presented at the 2023 American Society of Clinical Oncology Annual Meeting, demonstrate that spinal cord gliomas have unique molecular features, suggesting an underlying biology distinct from intracranial gliomas.

Chow recently spoke more about the study in an interview.

What prompted this study?  

Spinal cord gliomas are rare tumors. Because of the world-class specialists at the USC Spine Center and USC Brain Tumor Center, we see and treat many cases. But, despite standard therapies, spinal cord gliomas are challenging to manage because there remains no cure.

This study arose from our need to identify crucial therapeutic targets to develop novel treatment approaches for these tumors.

Why is the distinction between spinal cord gliomas and intercranial gliomas important?

No consensus guidelines exist for the management of spinal cord gliomas. The current clinical management of spinal cord gliomas is drawn from our experience with intracranial tumors.

However, we have increasing evidence that tumors from different regions of the central nervous system harbor unique molecular signatures and behave very differently from one another. 

What key biological differences between these types of tumors were discovered? 

In our study, the most common spinal tumor genetic alterations were H3K27M mutations and BRAF fusions. In fact, the canonical intracranial glioma alterations such as MGMT promoter methylation, TERT, EGFR or IDH mutations were rarely or never seen in spinal tumors.

We additionally analyzed key indicators of tumor aggressiveness (tumor epithelial mesenchymal transition) and immune cell infiltration.

How might the study inform new treatment approaches? 

We provide a biological explanation for the limited effectiveness of current therapies for spinal cord gliomas, with potential implications for novel approaches using chemotherapy and immunotherapy.

For example, MGMT promoter methylation — which predicts sensitivity to our first-line chemotherapy — is present in less than 30% of patients. This may explain our observations that standard chemotherapy has limited effectiveness in spinal gliomas. 

High grade spinal gliomas harbor RAF1 and PDGFRA alterations, which may guide potential targeted therapies. Spinal gliomas have higher B cell, Treg and dendritic cell infiltration, with higher IDO1 expression in high grade spinal gliomas. These results inform potential immunotherapy approaches.

What other implications does this research have for referring providers? 

Our work underscores the role of personalized medicine and the need for investigations dedicated uniquely to patients with spinal cord gliomas. We strive to continue advancing our knowledge and treatment options for spinal cord glioma patients.

At Keck Medicine, we tailor treatments for each patient’s tumor, and we offer clinical trials to bring novel therapies from the bench to the bedside.