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Molecular profiling of sacral chordomas through methylation, spatial transcriptomics and multiplexed
1Division of Precision Medicine, Department of Medicine, Grossman School of Medicine, New York University, New York.
ESMO Rare Cancers
|April 2, 2026
Summary
Sacral chordoma epigenetics reveal two clusters linked to recurrence. Immune checkpoint markers like PD-1 were found in tumor stroma, suggesting new therapeutic targets for this rare bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Chordomas are rare, slow-growing bone malignancies originating from notochord remnants, primarily affecting the sacrum and skull base.
- Despite low-grade histology, chordomas can exhibit local aggressiveness and high recurrence rates.
- Understanding chordoma molecular heterogeneity is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the molecular heterogeneity of sacral chordomas.
- To identify distinct epigenetic profiles and their association with tumor recurrence.
- To explore the tumor microenvironment, including immune cell infiltration and checkpoint marker expression.
Main Methods:
- Retrospective analysis of 29 sacral chordoma patient samples.
- DNA methylation profiling for epigenetic analysis.
- Digital Spatial Profiler (DSP) for transcriptomic analysis.
- Multiplexed immunofluorescence for immune cell profiling.
Main Results:
- Two distinct epigenetic clusters (Cluster1 and Cluster2) were identified via DNA methylation profiling, with Cluster2 associated with higher recurrence rates.
- Differential gene expression analysis revealed altered Major Histocompatibility Complex (MHC) class I and II gene expression between tumor and stromal regions.
- Stromal regions showed enrichment of immune-activated T cells and expression of immune checkpoint markers, including TIM3, CD47, and PD-1.
Conclusions:
- Distinct epigenetic profiles in sacral chordomas correlate with tumor recurrence.
- The expression of immune checkpoint markers (TIM3, CD47, PD-1) in the tumor microenvironment presents potential therapeutic targets.
- Further functional studies are warranted to validate these findings and explore therapeutic strategies.
