Molecular subtyping reveals immune alterations in IDH wild‐type lower‐grade diffuse glioma
Abstract
Abstract Isocitrate dehydrogenase ( IDH ) wild‐type diffuse lower‐grade glioma (LGG) is usually associated with poor outcome, but there have been disputes over its clinical outcome and classification. We present here a robust gene expression‐based molecular classification of IDH wild‐type diffuse LGG into two subtypes with distinct biological and clinical features. A discovery cohort of 49 IDH wild‐type diffuse LGGs from the Chinese Glioma Genome Atlas (CGGA) was subjected to clustering and function analysis. Seventy‐three tumors from The Cancer Genome Atlas (TCGA) were used to validate our findings. Consensus clustering of transcriptional data uncovered concordant classification of two robust and prognostically significant subtypes of IDH wild‐type LGG. Subtype 1, associated with poorer outcomes, was characterized by significantly higher immune and cytolytic scores, M2 macrophages, and up‐regulation of immune exhaustion markers, while Subtype 2, which had elevated lymphocytes and plasma cells, showed relatively favorable survival. Somatic alteration analysis revealed that Subtype 1 showed more frequently deleted regions, such as the locus of CDKN2A / CDKN2B , DMRTA1 , C9orf53 , and MTAP . Furthermore, we developed and validated a five‐gene signature for better application of this acquired stratification. Our data demonstrate the biological and prognostic heterogeneity within IDH wild‐type diffuse LGGsmore »
- Authors:
-
[1]
- Department of Molecular Neuropathology, Beijing Neurosurgical Institute Capital Medical University Beijing PR China, Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University Beijing PR China, Chinese Glioma Genome Atlas Network (CGGA) and Asian Glioma Genome Atlas Network (AGGA) Beijing PR China
- Department of Molecular Neuropathology, Beijing Neurosurgical Institute Capital Medical University Beijing PR China, Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University Beijing PR China
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1633475
- Resource Type:
- Publisher's Accepted Manuscript
- Journal Name:
- Journal of Pathology
- Additional Journal Information:
- Journal Name: Journal of Pathology Journal Volume: 251 Journal Issue: 3; Journal ID: ISSN 0022-3417
- Publisher:
- Wiley Blackwell (John Wiley & Sons)
- Country of Publication:
- United Kingdom
- Language:
- English
Citation Formats
Wu, Fan, Li, Guan‐Zhang, Liu, Han‐Jie, Zhao, Zheng, Chai, Rui‐Chao, Liu, Yu‐Qing, Jiang, Hao‐Yu, Zhai, You, Feng, Yue‐Mei, Li, Ren‐Peng, and Zhang, Wei. Molecular subtyping reveals immune alterations in IDH wild‐type lower‐grade diffuse glioma. United Kingdom: N. p., 2020.
Web. doi:10.1002/path.5468.
Wu, Fan, Li, Guan‐Zhang, Liu, Han‐Jie, Zhao, Zheng, Chai, Rui‐Chao, Liu, Yu‐Qing, Jiang, Hao‐Yu, Zhai, You, Feng, Yue‐Mei, Li, Ren‐Peng, & Zhang, Wei. Molecular subtyping reveals immune alterations in IDH wild‐type lower‐grade diffuse glioma. United Kingdom. https://doi.org/10.1002/path.5468
Wu, Fan, Li, Guan‐Zhang, Liu, Han‐Jie, Zhao, Zheng, Chai, Rui‐Chao, Liu, Yu‐Qing, Jiang, Hao‐Yu, Zhai, You, Feng, Yue‐Mei, Li, Ren‐Peng, and Zhang, Wei. Mon .
"Molecular subtyping reveals immune alterations in IDH wild‐type lower‐grade diffuse glioma". United Kingdom. https://doi.org/10.1002/path.5468.
@article{osti_1633475,
title = {Molecular subtyping reveals immune alterations in IDH wild‐type lower‐grade diffuse glioma},
author = {Wu, Fan and Li, Guan‐Zhang and Liu, Han‐Jie and Zhao, Zheng and Chai, Rui‐Chao and Liu, Yu‐Qing and Jiang, Hao‐Yu and Zhai, You and Feng, Yue‐Mei and Li, Ren‐Peng and Zhang, Wei},
abstractNote = {Abstract Isocitrate dehydrogenase ( IDH ) wild‐type diffuse lower‐grade glioma (LGG) is usually associated with poor outcome, but there have been disputes over its clinical outcome and classification. We present here a robust gene expression‐based molecular classification of IDH wild‐type diffuse LGG into two subtypes with distinct biological and clinical features. A discovery cohort of 49 IDH wild‐type diffuse LGGs from the Chinese Glioma Genome Atlas (CGGA) was subjected to clustering and function analysis. Seventy‐three tumors from The Cancer Genome Atlas (TCGA) were used to validate our findings. Consensus clustering of transcriptional data uncovered concordant classification of two robust and prognostically significant subtypes of IDH wild‐type LGG. Subtype 1, associated with poorer outcomes, was characterized by significantly higher immune and cytolytic scores, M2 macrophages, and up‐regulation of immune exhaustion markers, while Subtype 2, which had elevated lymphocytes and plasma cells, showed relatively favorable survival. Somatic alteration analysis revealed that Subtype 1 showed more frequently deleted regions, such as the locus of CDKN2A / CDKN2B , DMRTA1 , C9orf53 , and MTAP . Furthermore, we developed and validated a five‐gene signature for better application of this acquired stratification. Our data demonstrate the biological and prognostic heterogeneity within IDH wild‐type diffuse LGGs and deepen our molecular understandi‐g of this tumor entity. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.},
doi = {10.1002/path.5468},
journal = {Journal of Pathology},
number = 3,
volume = 251,
place = {United Kingdom},
year = {Mon Jun 15 00:00:00 EDT 2020},
month = {Mon Jun 15 00:00:00 EDT 2020}
}
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