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Multi-scale signaling and tumor evolution in high-grade gliomas
Jingxian Liu1, Song Cao1, Kathleen J Imbach2
1Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
Cancer Cell
|July 9, 2024
Summary
This study integrates multi-omics data to reveal molecular drivers in high-grade gliomas. Findings highlight PTPN11 signaling as a key player in tumor evolution and recurrence.
Area of Science:
- Neuro-oncology
- Cancer Genomics
- Systems Biology
Background:
- Glioblastoma (GBM) has a poor prognosis despite extensive genomic research.
- Understanding the molecular complexity of high-grade gliomas is crucial for improving patient outcomes.
Purpose of the Study:
- To expand the molecular understanding of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma.
- To integrate multi-omics data (proteomics, metabolomics, lipidomics, PTMs) with genomic and transcriptomic data.
- To uncover multi-scale regulatory interactions in high-grade glioma development and evolution.
Main Methods:
- Applied 14 proteogenomic and metabolomic platforms to 228 high-grade gliomas (212 GBM, 16 IDH-mutant astrocytoma) and comparator samples.
- Included primary tumors and samples at recurrence, alongside normal brain and brain metastases.
- Integrated multi-omics data with genomic and transcriptomic measurements.
Main Results:
- Identified heterogeneous upstream alterations converging on common downstream proteomic and metabolomic events.
- Observed changes in protein-protein interactions and glycosylation site occupancy at tumor recurrence.
- Found recurrent genetic alterations and phosphorylation events on PTPN11.
Conclusions:
- PTPN11 signaling plays a central role across high-grade gliomas.
- Multi-scale molecular profiling reveals key regulatory interactions in glioma.
- Understanding these interactions is vital for developing targeted therapies.
Keywords:
CPTACglioblastomaglycoproteomicslipidomemetabolomeproteomicssingle nuclei ATAC-seqsingle nuclei RNA-seqtumor recurrenceMore Related Videos
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