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A glioma classifica...
A glioma classification scheme based on coexpression modules of EGFR and PDGFRA
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- Sun, Yingyu (author)
- Beijing Normal University
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- Zhang, Wei (author)
- Capital University of Medical Sciences
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- Chen, Dongfeng (author)
- Lund University,Lunds universitet,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Rausing laboratory of Lund - Tumor section,Lund University Research Groups
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- Lv, Yuhong (author)
- Beijing Normal University
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- Zheng, Junxiong (author)
- Beijing Normal University
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- Lilljebjörn, Henrik (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine
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- Ran, Liang (author)
- Beijing Normal University
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- Bao, Zhaoshi (author)
- Capital University of Medical Sciences
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- Soneson, Charlotte (author)
- Lund University,Lunds universitet,Matematikcentrum,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Mathematical Sciences,Departments at LTH,Faculty of Engineering, LTH
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- Olov Sjögren, Hans (author)
- Lund University,Lunds universitet,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Rausing laboratory of Lund - Tumor section,Lund University Research Groups
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- Salford, Leif G. (author)
- Lund University,Lunds universitet,Rausinglaboratoriet i Lund - Tumörsektionen,Forskargrupper vid Lunds universitet,Rausing laboratory of Lund - Tumor section,Lund University Research Groups
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- Ji, Jianguang (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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- Frenc, Pim J. (author)
- Erasmus University Medical Center
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- Fioretos, Thoas (author)
- Lund University,Lunds universitet,Matematikcentrum,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Mathematical Sciences,Departments at LTH,Faculty of Engineering, LTH
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- Jiang, Tao (author)
- Capital University of Medical Sciences
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- Fan, Xiaolong (author)
- Beijing Normal University
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(creator_code:org_t)
- 2014-02-18
- 2014
- English 6 s.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 111:9, s. 3538-3543
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Abstract
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- We hypothesized that key signaling pathways of glioma genesis might enable the molecular classification of gliomas. Gene coexpression modules around epidermal growth factor receptor (EGFR) (EM, 29 genes) or platelet derived growth factor receptor A (PDGFRA) (PM, 40 genes) in gliomas were identified. Based on EM and PM expression signatures, nonnegative matrix factorization reproducibly clustered 1,369 adult diffuse gliomas WHO grades II-IV from four independent databases generated in three continents, into the subtypes (EM, PM and EMlowPMlow gliomas) in a morphology-independent manner. Besides their distinct patterns of genomic alterations, EM gliomas were associated with higher age at diagnosis, poorer prognosis, and stronger expression of neural stem cell and astrogenesis genes. Both PM and EMlowPMlow gliomas were associated with younger age at diagnosis and better prognosis. PM gliomas were enriched in the expression of oligodendrogenesis genes, whereas EMlowPMlow gliomas were enriched in the signatures of mature neurons and oligodendrocytes. The EM/PM-based molecular classification scheme is applicable to adult low-grade and high-grade diffuse gliomas, and outperforms existing classification schemes in assigning diffuse gliomas to subtypes with distinct transcriptomic and genomic profiles. The majority of the EM/PM classifiers, including regulators of glial fate decisions, have not been extensively studied in glioma biology. Subsets of these classifiers were coexpressed in mouse glial precursor cells, and frequently amplified or lost in an EM/PM glioma subtypespecific manner, resulting in somatic copy number alteration-dependent gene expression that contributes to EM/PM signatures in glioma samples. EM/PM-based molecular classification provides a molecular diagnostic framework to expedite the search for new glioma therapeutic targets.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Sun, Yingyu
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Zhang, Wei
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Chen, Dongfeng
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Lv, Yuhong
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Zheng, Junxiong
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Lilljebjörn, Hen ...
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show more...
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Ran, Liang
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Bao, Zhaoshi
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Soneson, Charlot ...
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Olov Sjögren, Ha ...
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Salford, Leif G.
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Ji, Jianguang
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Frenc, Pim J.
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Fioretos, Thoas
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Jiang, Tao
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Fan, Xiaolong
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Proceedings of t ...
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Proceedings of t ...
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Lund University