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| Status |
Public on Jan 02, 2023 |
| Title |
Epigenetic reprogramming shapes the cellular landscape of schwannoma, DNA Methylation |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Cell state evolution underlies tumor development and response to therapy, but mechanisms specifying cancer cell states and intratumor heterogeneity are incompletely understood. Schwannomas are the most common tumors of the peripheral nervous system and are treated with surgery and ionizing radiation. Schwannomas can oscillate in size for many years after radiotherapy, suggesting treatment may reprogram schwannoma cells or the tumor microenvironment. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas. We find schwannomas are comprised of 2 methylation based molecular groups distinguished by reactivation of neural crest development pathways or misactivation of nerve injury mechanisms that specify cancer cell states and the architecture of the tumor immune microenvironment. Schwannoma molecular groups can arise independently, but ionizing radiation is sufficient for epigenetic reprogramming of neural crest to immune-enriched schwannoma by remodeling chromatin accessibility, gene expression, and metabolism to drive schwannoma cell state evolution and immune cell infiltration. To define functional genomic mechanisms underlying epigenetic reprograming of schwannomas, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of cancer evolution and establish a paradigm of epigenetic reprograming of cancer in response to radiotherapy.
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| Overall design |
illumina EPIC methylation profiles of vestibular schwannomas.
Note: the 'classification' samples (i.e. VS*, HEI193* samples) were only used as raw input data for a support vector machine classifier so only clinical tumor (S*) processed data are provided here.
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| Contributor(s) |
Liu SJ, Raleigh D |
| Citation(s) |
38216587 |
| |
| Submission date |
Jan 02, 2023 |
| Last update date |
Jan 29, 2024 |
| Contact name |
John Liu |
| E-mail(s) |
john.liu@ucsf.edu
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| Organization name |
UCSF
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| Street address |
35 Medical Center Way
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| City |
SAN FRANCISCO |
| State/province |
California |
| ZIP/Postal code |
94143 |
| Country |
USA |
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| Platforms (1) |
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| Samples (81)
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| Relations |
| BioProject |
PRJNA917427 |
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