Molecular mechanisms involved in gliomagenesis

The application of molecular parameters in the World Health Organization classification of central nervous system tumors has advanced remarkably in this field. Large-scale genomic DNA analyses, including gene expression profiling, genome-wide association studies, and single-nucleotide polymorphism analysis, have revealed differences between tumors with the same pathological features. Because mutated genes and their signaling pathways can be targets for therapy, categorizing tumors by molecular parameters facilitates the selection of optimal therapeutic methods. Many genes are either oncogenes or tumor suppressor genes, and many of them are also involved in normal development, such as neural stem cell maintenance and neural differentiation. Moreover, genetic engineering has enabled the generation of tumors that phenocopy human tumors in mice. Here, I will discuss key molecular parameters, mechanisms of neural differentiation, isocitrate dehydrogenases, 1p36/19q13, and p53 in gliomagenesis. Because future therapeutic methods will be determined by the molecular mechanisms of tumors, identification of new parameters is still needed for further classification of glioma.

[1]  Andrew P. McMahon,et al.  Sonic hedgehog Regulates Proliferation and Inhibits Differentiation of CNS Precursor Cells , 1999, The Journal of Neuroscience.

[2]  W. Richardson,et al.  Summary Roles for p 53 and p 73 during oligodendrocyte development , 2004 .

[3]  Fred H. Gage,et al.  Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo , 2003, Nature Neuroscience.

[4]  John D. Heiss,et al.  New Developments in the Pathogenesis and Therapeutic Targeting of the IDH1 Mutation in Glioma , 2015, International journal of medical sciences.

[5]  G. Reifenberger,et al.  Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. , 1994, The American journal of pathology.

[6]  S. Ohue,et al.  Eva 1 Maintains the Stem-like Character of Glioblastoma-Initiating Cells by Activating the Noncanonical NFk B Signaling Pathway , 2015 .

[7]  S. Inoue,et al.  D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function. , 2012, Genes & development.

[8]  Angelo L. Vescovi,et al.  bFGF regulates the proliferative fate of unipotent (neuronal) and bipotent (neuronal/astroglial) EGF-generated CNS progenitor cells , 1993, Neuron.

[9]  Angelo L. Vescovi,et al.  Brain tumour stem cells , 2006, Nature Reviews Cancer.

[10]  Liu Cao,et al.  PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma , 2016, Oncotarget.

[11]  Frank M. Sacks,et al.  IDH 1 and IDH 2 Mutations in Gliomas , 2009 .

[12]  W. Gerald,et al.  Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts , 1999, Nature.

[13]  Kun-Liang Guan,et al.  Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1α , 2009, Science.

[14]  G. Reifenberger,et al.  The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary , 2016, Acta Neuropathologica.

[15]  J. Uhm.  An Integrated Genomic Analysis of Human Glioblastoma Multiforme , 2009 .

[16]  M. Raff,et al.  The Id4 HLH protein and the timing of oligodendrocyte differentiation , 2000, The EMBO journal.

[17]  M. Waterfield,et al.  Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. , 1988, Nature.

[18]  M. Greenberg,et al.  Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway. , 1997, Science.

[19]  M. Resh,et al.  Tyrosine phosphorylation of p190 RhoGAP by Fyn regulates oligodendrocyte differentiation. , 2001, Journal of neurobiology.

[20]  Junnian Zheng,et al.  p53-mediated autophagic regulation: A prospective strategy for cancer therapy. , 2015, Cancer letters.

[21]  H. Vogel,et al.  CHD5 Is a Tumor Suppressor at Human 1p36 , 2007, Cell.

[22]  M. Narita,et al.  Cellular senescence and its effector programs , 2014, Genes & development.

[23]  Yuan Qi,et al.  Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA , IDH 1 , EGFR , and NF 1 Citation Verhaak , 2010 .

[24]  H. Takebayashi,et al.  Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the astrocytic differentiation pathway , 2004, Cell Death and Differentiation.

[25]  T. Kondo.  Brain cancer stem-like cells. , 2006, European journal of cancer.

[26]  Y. Arsenijévic,et al.  Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice. , 2005, Genes & development.

[27]  K. Ueki.  Oligodendroglioma: Impact of molecular biology on its definition, diagnosis and management , 2005, Neuropathology : official journal of the Japanese Society of Neuropathology.

[28]  Eva-Maria Krämer-Albers,et al.  From axon–glial signalling to myelination: the integrating role of oligodendroglial Fyn kinase , 2011, Cellular and Molecular Life Sciences.

[29]  J. Arbiser,et al.  Targeting NADPH oxidases for the treatment of cancer and inflammation , 2012, Cellular and Molecular Life Sciences.

[30]  W. Richardson,et al.  A role for platelet-derived growth factor in normal gliogenesis in the central nervous system , 1988, Cell.

[31]  S. Ohue,et al.  Eva1 Maintains the Stem-like Character of Glioblastoma-Initiating Cells by Activating the Noncanonical NF-κB Signaling Pathway. , 2016, Cancer Research.

[32]  W. Richardson,et al.  Platelet-derived growth factor from astrocytes drives the clock that times oligodendrocyte development in culture , 1988, Nature.

[33]  Qun-ying Yang,et al.  Mutation of isocitrate dehydrogenase 1 induces glioma cell proliferation via nuclear factor-κB activation in a hypoxia-inducible factor 1-α dependent manner. , 2014, Molecular medicine reports.

[34]  K. Houkin,et al.  Ceacam1L Modulates STAT3 Signaling to Control the Proliferation of Glioblastoma-Initiating Cells. , 2015, Cancer research.

[35]  Hideo Nakamura,et al.  Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation. , 2009, Cancer research.

[36]  P. Verrelle,et al.  Role of Akt in human malignant glioma: from oncogenesis to tumor aggressiveness , 2014, Journal of Neuro-Oncology.

[37]  M. Resh,et al.  p190RhoGAP can act to inhibit PDGF-induced gliomas in mice: a putative tumor suppressor encoded on human chromosome 19q13.3. , 2003, Genes & development.

[38]  J D Norton,et al.  ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. , 2000, Journal of cell science.

[39]  P. Cochard,et al.  Bone morphogenetic proteins negatively control oligodendrocyte precursor specification in the chick spinal cord. , 2002, Development.

[40]  S. Weiss,et al.  Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. , 1992, Science.

[41]  Joshua M. Korn,et al.  Comprehensive genomic characterization defines human glioblastoma genes and core pathways , 2008, Nature.

[42]  F. Gage,et al.  Mammalian neural stem cells. , 2000, Science.

[43]  S. M. Reed,et al.  p53 Acetylation: Regulation and Consequences , 2014, Cancers.

[44]  S. Berger,et al.  IDH mutation impairs histone demethylation and results in a block to cell differentiation , 2012, Nature.

[45]  Pieter Wesseling,et al.  Oligodendroglioma: pathology, molecular mechanisms and markers , 2015, Acta Neuropathologica.

[46]  J. Heymach,et al.  Multiple receptor tyrosine kinases regulate HIF-1α and HIF-2α in normoxia and hypoxia in neuroblastoma: implications for antiangiogenic mechanisms of multikinase inhibitors , 2010, Oncogene.

[47]  L. Pevny,et al.  SOX2 Functions to Maintain Neural Progenitor Identity , 2003, Neuron.

[48]  Flore Kruiswijk,et al.  p53 in survival, death and metabolic health: a lifeguard with a licence to kill , 2015, Nature Reviews Molecular Cell Biology.

[49]  P. Dirks,et al.  Cancer stem cells in nervous system tumors , 2004, Oncogene.

[50]  Sally Temple,et al.  The development of neural stem cells , 2001, Nature.

[51]  S. Morrison,et al.  Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. , 2005, Genes & development.

[52]  Pierre Hainaut,et al.  Massively regulated genes: the example of TP53 , 2010, The Journal of pathology.

[53]  K. Miyazono,et al.  Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. , 1999, Science.

[54]  C. Anderson,et al.  Posttranslational modification of p53: cooperative integrators of function. , 2009, Cold Spring Harbor perspectives in biology.

[55]  K. Ikenaka,et al.  Wnt signaling controls the timing of oligodendrocyte development in the spinal cord. , 2005, Developmental biology.

[56]  S. Ohue,et al.  miR340 suppresses the stem-like cell function of glioma-initiating cells by targeting tissue plasminogen activator. , 2015, Cancer research.

[57]  R. McLendon,et al.  IDH1 and IDH2 mutations in gliomas. , 2009, The New England journal of medicine.