The DOI matches its Crossref record; 93 of the 93 references it cites were found in a registry or an index.
Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities
Open accessAbstract
Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities. Merlin-intact meningiomas (34%) have the best outcomes and are distinguished by NF2/Merlin regulation of susceptibility to cytotoxic therapy. Immune-enriched meningiomas (38%) have intermediate outcomes and are distinguished by immune infiltration, HLA expression and lymphatic vessels. Hypermitotic meningiomas (28%) have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. To translate these findings into clinical practice, we show cytostatic cell cycle inhibitors attenuate meningioma growth in cell culture, organoids, xenografts and patients. DNA methylation profiling of 565 meningiomas highlights three groups associated with distinct molecular, clinical and therapeutic features.
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Cited by
Horbinski, C., Berger, T., Packer, R. J., & Wen, P. Y. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00679-w · Cited by 312
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Metadata
- Authors
- Choudhury, A., Magill, S. T., Eaton, C. D., Prager, B. C., Chen, W. C., Cady, M. A., Seo, K., Lucas, C.-H. G., Casey-Clyde, T. J., Vasudevan, H. N., Liu, S. J., Villanueva-Meyer, J. E., Lam, T.-C., Pu, J. K.-S., Li, L.-F., Leung, G. K.-K., Swaney, D. L., Zhang, M. Y., Chan, J. W., Qiu, Z., Martin, M. V., Susko, M. S., Braunstein, S. E., Bush, N. A. O., Schulte, J. D., Butowski, N., Sneed, P. K., Berger, M. S., Krogan, N. J., Perry, A., Phillips, J. J., Solomon, D. A., Costello, J. F., McDermott, M. W., Rich, J. N., & Raleigh, D. R.
- Venue
- Nature Genetics
- Published
- 2022-05
- Volume
- 54
- Issue
- 5
- Pages
- 649-659
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W4229449309
- Cited by
- 293
- References
- 93
- FWCI
- 36.74
- Type
- journal article
- Language
- en
- Open access
- green
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- Choudhury, A., Magill, S. T., Eaton, C. D., Prager, B. C., Chen, W. C., Cady, M. A., Seo, K., Lucas, C.-H. G., Casey-Clyde, T. J., Vasudevan, H. N., Liu, S. J., Villanueva-Meyer, J. E., Lam, T.-C., Pu, J. K.-S., Li, L.-F., Leung, G. K.-K., Swaney, D. L., Zhang, M. Y., Chan, J. W., . . . Raleigh, D. R. (2022). Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities. Nature Genetics. https://doi.org/10.1038/s41588-022-01061-8
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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