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Exploration of Involved Key Genes and Signaling Diversity in Brain Tumors

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Abstract

Brain tumors are becoming a major cause of death. The classification of brain tumors has gone through restructuring with regard to some criteria such as the presence or absence of a specific genetic alteration in the 2016 central nervous system World Health Organization update. Two categories of genes with a leading role in tumorigenesis and cancer induction include tumor suppressor genes and oncogenes; tumor suppressor genes are inactivated through a variety of mechanisms that result in their loss of function. As for the oncogenes, overexpression and amplification are the most common mechanisms of alteration. Important cell cycle genes such as p53, ATM, cyclin D2, and Rb have shown altered expression patterns in different brain tumors such as meningioma and astrocytoma. Some genes in signaling pathways have a role in brain tumorigenesis. These pathways include hedgehog, EGFR, Notch, hippo, MAPK, PI3K/Akt, and WNT signaling. It has been shown that telomere length in some brain tumor samples is shortened compared to that in normal cells. As the shortening of telomere length triggers chromosome instability early in brain tumors, it could lead to initiation of cancer. On the other hand, telomerase activity was positive in some brain tumors. It is suggestive that telomere length and telomerase activity are important diagnostic markers in brain tumors. This review focuses on brain tumors with regard to the status of oncogenes, tumor suppressors, cell cycle genes, and genes in signaling pathways as well as the role of telomere length and telomerase in brain tumors.

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Abbreviations

2-CA:

2-Chloro-adenosine

2-CdA:

2-Chloro-2′-deoxyadenosine

ALP:

Alkaline phosphatases

ALT:

Alternative lengthening of telomeres

Apyrase:

Adenyl-pyrophosphatase

ATM:

Ataxia telangiectasia mutated

ATP:

Adenosine 5′-triphosphate

ATRX:

Alpha thalassemia/mental retardation syndrome X-linked

bHLH:

Basic helix-turn-helix

CD39:

Ectonucleoside triphosphate diphosphohydrolase-1

CD73:

Ecto-5′-nucleotidase

CNS:

Central nervous system

CSC:

Cancer stem cell

D-2HG:

D2-hydroxyglutarate

DAG:

Diacylglycerol

DAXX:

Death-domain associated protein

DDR:

DNA damage response

DHH:

Desert hedgehog

E-NPPases:

Ectonucleoside pyrophosphatase/phosphodiesterases

E-NTPDases:

Ectonucleoside triphosphate diphosphohydrolases

EAE:

Experimental autoimmune encephalomyelitis

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-to-mesenchymal transition

EPL:

Early progenitor-like

GBM:

Glioblastoma multiform

G-CIMP:

Glioma-CpG island methylator phenotype

GSK-3β:

Glycogen synthase kinase 3 beta

HIF:

Hypoxia-inducible factor

HTERT:

Human telomerase reverse transcriptase

IHC:

Immunohistochemistry

IHH:

Indian hedgehog

IL-6:

Interleukin-6

IL-8:

Interleukin-8

IP3:

Inositol-1,4,5-triphosphate

LOH:

Loss of heterozygosity

MB:

Medulloblastoma

MBEN:

Medulloblastoma with extensive nodularity

MET:

Mesenchymal-to-epithelial transition

MMP2:

Matrix metalloproteinase-2

MMP9:

Matrix metalloproteinase-9

NB:

Neuroblastic

PET:

Positron emission tomography

PDGF:

Platelet-derived growth factor

PDGFR:

Platelet-derived growth factor receptor

PG:

Pre-glioblastoma

PHDs:

Prolyl hydroxylase domain proteins

PIP2 :

Phosphatidylinositol 4,5-bisphosphate

PIP3 :

Phosphatidylinositol 3,4,5-trisphosphate

PKA:

Protein kinase A

PKB:

Protein kinase B

PKC:

Protein kinase C

PLGG:

Pediatric low-grade glioblastoma

Q-FISH:

Quantitative fluorescent in situ hybridization

RT-PCR:

Reverse transcription polymerase chain reaction

sHGG:

Secondary high-grade glioblastoma

SHH:

Sonic hedgehog

SMO:

Smoothened

SUFU:

Suppressor of fused homolog

TCF/LEF:

T-cell factor/lymphoid enhancer factor

TNFα:

Tumor necrosis factor alpha

TMZ:

Temozolomide

TRAP assay:

Telomeric repeat amplification protocol assay

TRF:

Terminal restriction fragment

WHO:

World Health Organization

YAP1:

Yes-associated protein 1

α-KG:

α-Ketoglutarate

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  1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mojdeh Mahdian Nasser & Parvin Mehdipour

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Nasser, M.M., Mehdipour, P. Exploration of Involved Key Genes and Signaling Diversity in Brain Tumors. Cell Mol Neurobiol 38, 393–419 (2018). https://doi.org/10.1007/s10571-017-0498-9

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