Molecular and cellular heterogeneity: the hallmark of glioblastoma

被引:156
作者
Aum, Diane J. [1 ]
Kim, David H. [1 ]
Beaumont, Thomas L. [1 ]
Leuthardt, Eric C. [1 ,5 ,6 ,9 ,10 ]
Dunn, Gavin P. [1 ,4 ,7 ,8 ,10 ]
Kim, Albert H. [1 ,2 ,3 ,9 ,10 ]
机构
[1] Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA
[4] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[5] Washington Univ, Sch Med, Dept Biomed Engn, St Louis, MO 63110 USA
[6] Washington Univ, Sch Med, Dept Mech & Mat Sci, St Louis, MO 63110 USA
[7] Washington Univ, Sch Med, Ctr Human Immunol, St Louis, MO 63110 USA
[8] Washington Univ, Sch Med, Immunotherapy Programs, St Louis, MO 63110 USA
[9] Washington Univ, Sch Med, Ctr Innovat Neurosci & Technol, St Louis, MO 63110 USA
[10] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
关键词
glioblastoma; glioma; genomic; heterogeneity; IDH1; INTEGRATED GENOMIC ANALYSIS; IDH1; MUTATION; ONCOMETABOLITE; 2-HYDROXYGLUTARATE; INTRATUMORAL HETEROGENEITY; STEM-CELLS; TUMOR; EVOLUTION; GLIOMA; EGFR; DIFFERENTIATION;
D O I
10.3171/2014.9.FOCUS14521
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
There has been increasing awareness that glioblastoma, which may seem histopathologically similar across many tumors, actually represents a group of molecularly distinct tumors. Emerging evidence suggests that cells even within the same tumor exhibit wide-ranging molecular diversity. Parallel to the discoveries of molecular heterogeneity among tumors and their individual cells, intense investigation of the cellular biology of glioblastoma has revealed that not all cancer cells within a given tumor behave the same. The identification of a subpopulation of brain tumor cells termed "glioblastoma cancer stem cells" or "tumor-initiating cells" has implications for the management of glioblastoma. This focused review will therefore summarize emerging concepts on the molecular and cellular heterogeneity of glioblastoma and emphasize that we should begin to consider each individual glioblastoma to be an ensemble of molecularly distinct subclones that reflect a spectrum of dynamic cell states.
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页数:11
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