Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. Temozolomide (TMZ) is the most widely used chemotherapeutic agent and can significantly improve patient survival rates. However, numerous patients develop TMZ resistance, leading to limited therapeutic benefits. Therefore, it is crucial to investigate the mechanisms of TMZ resistance in patients with GBM and identify the sensitizing targets of TMZ to improve its clinical efficacy. In this study, we demonstrated that acylphosphatase 2 (ACYP2) was involved in regulating the sensitivity of GBM to TMZ. ACYP2 knockdown significantly reduced the IC50 values of TMZ in GBM cells, whereas overexpression of ACYP2 increased their IC50 values. The combination of ACYP2 knockdown and TMZ treatment not only inhibited the malignant behavior of GBM cells in vitro but also slowed the progression of intracranial GBM in mice. Additionally, comet tail and γ-H2AX staining assays showed that ACYP2 knockdown enhanced the TMZ-induced DNA damage. Mechanistically, ACYP2 upregulates the transcription factor c-Myc to promote the transcription of its downstream target PARP1, an important regulatory molecule for DNA damage repair, ultimately inducing TMZ resistance in GBM cells. Thus, this study demonstrated that ACYP2 is a potential therapeutic target for TMZ-resistant patients with GBM. IMPLICATIONS:The ACYP2-driven c-Myc/PARP1 signaling axis defines a critical pathway driving TMZ resistance and represents a translationally actionable target for therapeutic intervention in GBM.

BRAFV600E mutation is frequently found in human cancers particularly thyroid cancer and melanoma, and is involved in the regulation of gene expression through activating MAPK/Erk signaling. Trimethylation of histone 3 lysine 27 (H3K27me3) is a critical epigenetic mark for the maintenance of gene silencing in tumorigenesis. However, molecular mechanism underlying the complex interplay between these two molecular events remains to be explored. In the present study, we conducted chromatin immunoprecipitation combined with next-generation sequencing (ChIP-Seq) and expression microarray analysis in NIH3T3 cells to explore the relationship between H3K27me3 and transcriptional regulation by BRAFV600E mutation. Our results showed that activated MAPK/Erk signaling by BRAFV600E mutation was a trigger of this epigenetic processing at many downstream target genes in cancer cell lines and BrafV600E-induced thyroid cancer of transgenetic mice. By integrating ChIP-Seq and gene expression microarray data, we identified 150 down-regulated loci with increased levels of H3K27me3 in BRAF-mutant cells relative to BRAF wild-type cells. Our data also demonstrated that c-Myc, a downstream key effector of BRAFV600E signaling, was required for BRAFV600E-induced changes in H3K27me3 through regulating the components of the polycomb repressive complex 2 (PRC2) genes Ezh2, Suz12 and Jarid2 at both transcriptional levels via direct binding to their regulatory elements and post-transcriptional levels via repressing the miR-26a, miR-200b and miR-155. In addition, BRAFV600E also caused gene silencing through Erk1/2-induced RNA polymerase II (RNAPII) poising and chromatin architecture. Collectively, our data uncover a previously unknown epigenetic mechanism in the tumorigenesis of BRAFV600E-driven cancers.

Research has showed that the expression of MMP-8 was upregulated in osteoarthritis cartilage than in healthy controls. And one study has described that MMP-8 polymorphisms might associated with decreased risk of osteoarthritis in a Finnish population. Thus, we analyzed whether these variants also contribute to osteoarthritis susceptibility in a Chinese Han population. Sequenom MassARRAY Assay was used to determine the genotype of 300 osteoarthritis patients and 428 healthy controls from Northwest China. Fisher's exact test/Chi-square test was used to compare the differences of the investigated SNPs (rs3740938, rs2012390, rs1940475, and rs11225395) allele and genotype distribution between osteoarthritis cases and controls. After that, the correlation between each SNP and osteoarthritis risk was assessed under multiple genetic models analysis and haplotype analysis. No significant difference was observed for the allele and genotype distribution of the four SNPs between cases and controls. Analysis of the genetic models and haplotype block also failed to reveal any significant association (P>0.05). Our present case-control study is the first to explore the potential correlation between MMP-8 polymorphisms and osteoarthritis risk in a Chinese Han population. Though, negative results we got, further study is still required to validate the potential association in other populations and a larger sample size.

Inflammatory gene polymorphisms may be associated with glioma risk. The purpose of this study was to analyze effects of certain inflammatory gene and some clinical factors on patient survival.The clinical information of 269 glioma patients conceived operation from September 2010 to May 2014 to decide the 1-, 3-year survival rates according to follow-up results and analyze age, gender, the WHO classification, extent of surgical resection, radiotherapy and chemotherapy factors effects on prognosis. Survival distributions were estimated by using the Kaplan-Meier method and difference in the survival was tested using the log-rank test. To estimate the association between the IL4, IL13, IL10, IL4R SNPs, and PFS and OS in glioma, the HR and 95% CI were calculated by univariate Cox proportional hazards model. Multivariate Cox model were performed to compute adjusted HR and 95% CI. All data was analyzed with SPSS17.0 package. Extent of surgical resection, chemotherapy, and age are an important factor in glioma overall survival and progression-free survival overall. Extent of surgery and chemotherapy are important factors in astrocytoma overall survival. Univariate analysis showed that IL4R rs1801275 was significantly associated with overall survival of glioma and astrocytoma patients (P < 0.05). Multivariate Cox regression analysis showed that IL4R rs1801275 GG genotype could increase the death risk of glioma and astrocytoma patients (Glioma: hazard ratio [HR]: 4.897, 95% confidence limits [95% CI]: 1.962-12.222, P = 0.001; Astrocytoma: HR: 15.944, 95% CI: 4.019-63.253, P < 0.05).Our research results showed that extent of surgical resection, age, and chemotherapy affect the prognosis of glioma. The IL4R gene may affect the survival of glioma patients.

Objectives To increase the sensitivity of glioma stem cells to chemotherapeutic drugs by inducing atypical protein kinase C (aPKC) gene silence and to provide theoretical support for radical cure of glioma stem cells.Methods The side population cells in rat C6 glioblastoma were isolated by a flow cytometry.The expression of aPKC in C6 side population cells was silenced by RNA interference (RNAi) technology.MTT and trypan blue assay were used to detect the killing effect of herpes simplex virus-thymidine kinase (HSV-tk)/ ganciclovir (GCV) on C6 side population cells.A subcutaneous glioma model in nude rats was induced.The volume and weight of glioma were measured.In situ apoptosis assay was used to detect cell apoptosis.Results After the aPKC genes in C6 side population cells being effectively silenced,they could significantly increase their sensitivity to HSV-tk/GCV drugs.They showed apoptosis and the number of death increased significantly (P ＜ 0.05).The in vivo experiment showed that the volume and weight of glioma decreased significantly compared with the control group (P ＜ 0.05).The cell apoptosis increased significantly (P ＜ 0.05).Condusion By inducing aPKC gene silencing,it nay further increase the glioma stem cells to the sensitivity of chemotherapy drug HSV-tk/GCV and provide a new s election method for gene therapy of glioma stem cells.

Objective To study the neuroprotection mechanism of mild hypothermia using a neuronal injury model and protein two-dimensional gel electrophoresis.Methods A neuron damage model was induced by the cell lysates soak assay.Neurons were cultured in temperature-controlled incubator at 33 ℃ and 37 ℃ respectively.The lactic acid dehydrogenase level in the culture supernatant was tested.TUNEL apoptosis assay was use to compare the cell apoptosis under the 2 culture temperatures.The total cellular protein was extracted.The protein two-dimensional gel electrophoresis technique was used to screen the differential protein spots.Mass spectrometry was used to complete the protein identification.Western blot was used to conduct protein confirmation.Statistical methods were used to analyze the test results.Results The impaired neuronal lactate dehydrogenase level and the cell numbers of occurring in situ apoptosis were significantly lower than those of the 37 ℃ culture group under the low temperature condition (P ＜ 0.05).A total of 14 differential protein spots were screened using the two-dimensional gel electrophoresis,12 of them were identified effectively.They were involved in a variety of pathophysiological processes,including cellular energy metabolism,regeneration,and oxidative stress.Conclusion Mild hypothermia plays a certain neuroprotective effect by intervening and regulating multiple molecular events,including cellular energy metabolism,regeneration,and oxidative stress.

Epidemiological studies have demonstrated that leukocyte telomere length is associated with the developing risk of various malignancies, including glioma. However, its prognostic value in glioma patients has never been investigated.

BACKGROUND:Zinc transporters have been considered as essential regulators in many cancers; however, their mechanisms remain unknown, especially in gliomas. Isocitrate dehydrogenase 1(IDH1) mutation is crucial to glioma. This study aimed to investigate whether zinc transporters are correlated with glioma grade and IDH1 mutation status.MATERIALS AND METHODS:IDH1 mutation status and mRNA expression of four zinc transporters (ZIP4, ZIP9, ZIP11, and ZnT9) were determined by subjecting a panel of 74 glioma tissue samples to quantitative real-time PCR and pyrosequencing. The correlations between the expression levels of these zinc transporter genes and the grade of glioma, as well as IDH1 mutation status, were investigated.RESULTS:Among the four zinc transporter genes, high ZIP4 expression and low ZIP11 expression were significantly associated with higher grade (grades III and IV) tumors compared with lower grade (grades I and II) counterparts (p<0.0001). However, only ZIP11 exhibited weak correlation with IDH1 mutation status (p=0.045). Samples with mutations in IDH1 displayed higher ZIP11 expression than those without IDH1 mutations.CONCLUSIONS:This finding indicated that zinc transporters may interact with IDH1 mutation by direct modulation or action in some shared pathways or genes to promote the development of glioma. Zinc transporters may play an important role in glioma. ZIP4 and ZIP11 are promising molecular diagnostic markers and novel therapeutic targets. Nevertheless, the detailed biological function of zinc transporters and the mechanism of the potential interaction between ZIP11 and IDH1 mutation in gliomagenesis should be further investigated.

Objective Explore the application of microsurgical technique via transcallosal approach in the treatment of thalamic hemorrhage.Methods the clinical data of 25 patients with thalamic hemorrhage who were treated by haematoma evacuation by microscope via transcallosal approach in neurosurgery of our department from January 2010 to January 2013,the operation result and prognosis were collected.Results There is no patient suffered from intracranial infection and rebleeding after operation.20 patients survived after 3 months.The Barthel Index evaluation:BI ＞ 60(independent living) in 5 cases; 40 ＜ BI ＜ 60 (severe dysfunction) in 9 cases; 40 ＜ BI ＜ 20 (Moderate dysfunction) in 4 cases ; BI ＜ 20 (total disability)in 2 cases.Conclusion The microsurgical technique via transcallosal approach can remove thalamic hemorrhage effectively,and cause low postoperative complications.It is a feasible surgical technique for treatment of thalamic hemorrhage.

BACKGROUNDGlioblastoma (GBM) is an immunosuppressive tumor whose median survival time is only 12- 15 months, and patients with GBM have a uniformly poor prognosis. It is known that heredity contributes to formation of glioma, but there are few genetic studies concerning GBM.MATERIALS AND METHODSWe genotyped six tagging SNPs (tSNP) in Han Chinese GBM and control patients. We used Microsoft Excel and SPSS 16.0 statistical package for statistical analysis and SNP Stats to test for associations between certain tSNPs and risk of GBM in five different models. ORs and 95%CIs were calculated for unconditional logistic-regression analysis with adjustment for age and gender. The SHEsis software platform was applied for analysis of linkage disequilibrium, haplotype construction, and genetic associations at polymorphism loci.RESULTSWe found rs891835 in CCDC26 to be associated with GBM susceptibility at a level of p=0.009. The following genotypes of rs891835 were found to be associated with GBM risk in four different models of gene action: i) genotype GT (OR=2.26; 95%CI, 1.29-3.97; p=0.019) or GG (OR=1.33; 95%CI, 0.23-7.81; p=0.019) in the codominant model; ii) genotypes GT and GG (OR=2.18; 95%CI, 1.26-3.78; p=0.0061) in the dominant model; iii) GT (OR=2.24; 95%CI, 1.28-3.92; p=0.0053) in the overdominant model; iv) the allele G of rs891835 (OR=1.85; 95%CI, 1.14-3.00; p=0.015) in the additive model. In addition, "CG" and "CGGAG" were found by haplotype analysis to be associated with increased GBM risk. In contrast, genotype GG of CCDC26 rs6470745 was associated with decreased GBM risk (OR=0.34; 95%CI, 0.12-1.01; p=0.029) in the recessive model.CONCLUSIONSOur results, combined with those from previous studies, suggest a potential genetic contribution of CCDC26 to GBM progression among Han Chinese.

BACKGROUND:Increasing evidence suggests that alterations in mitochondrial DNA (mtDNA) content may be implicated in the tumorigenesis of several malignancies. However, the association between mtDNA content in peripheral blood lymphocytes (PBLs) and glioma risk has not been investigated.METHODS:Real-time PCR was used to examine the mtDNA content in PBLs of 414 glioma patients and 414 matched controls in a hospital-based case-control study. The association between mtDNA content and glioma risk was evaluated using an unconditional multivariate logistic regression model.RESULTS:We found that glioma patients exhibited a significantly higher median mtDNA content than healthy controls (0.99 vs. 0.71, P < 0.001). Unconditional multivariate logistic regression analysis adjusting for age, gender, smoking status, and family cancer history showed that there was an S-shaped association between mtDNA content and glioma risk. Higher mtDNA content was significantly associated with an elevated risk of glioma. Compared with the first quartile, the odds ratio (95% confidence interval) for subjects in the second, third, and fourth quartiles of mtDNA content were 0.90 (0.52-1.53), 3.38 (2.15-5.31), and 5.81 (3.74-9.03), respectively (P for nonlinearity = 0.009). Stratified analysis showed that the association between mtDNA content and glioma risk was not modulated by major host characteristics.CONCLUSIONS:Our findings demonstrate for the first time that a higher mtDNA content in PBLs is associated with an elevated risk of glioma, which warrants further investigation in larger populations.

Connexin 43 (Cx43) and aquaporin-4 (AQP4) have important roles in the formation of glioma-induced brain edema; however, the association between these two factors in the development of edema has remained to be elucidated. In the present study, immunofluorescence and western blot analysis revealed that in a rat model of intracranial C6 glioma, Cx43 expression levels were low to undetectable and AQP4 expression levels were low in glioma cells. Significantly higher Cx43 and AQP4 levels were detected in the tissue surrounding the glioma. To further investigate the potential interaction between Cx43 and AQP4, normal glial cells and C6 glioma cells were cultured in hypotonic medium. Reverse transcription quantitative polymerase chain reaction indicated that AQP4 and Cx43 mRNA expression levels increased as a function of time in normal glial cells and C6 glioma cells in a hypotonic environment. However, the increase observed in normal glial cells was significantly lower than that observed in C6 glioma cells. Furthermore, AQP4 expression levels changed prior to alterations in Cx43 expression. Following AQP4 silencing in C6 cells, the increase in Cx43 expression was significantly attenuated (P<0.05). In normal cells, Cx43 silencing did not influence AQP4 expression (P>0.05). Therefore, it was hypothesized that AQP4 and Cx43 had two distinct mechanisms underlying brain edema formation within and surrounding the glioma. Cx43 may be a downstream effector of AQP4. The elucidation of this pathway may aid in the development of drugs targeting the interaction between AQP4 and Cx43, providing novel therapeutic possibilities for glioma-induced brain edema.

Several recent studies have showed that the n-myc downstream regulated gene 2 (NDRG2) is a new tumor suppressor gene, and that it plays an important role in tumor suppression in several cancers or cancer cell lines. However, few studies focused on its function in neuroblastoma cells. In the present investigation, we demonstrated that NDRG2 overexpression inhibited their proliferation. Using a cDNA microarray, we found that overexpression of NDRG2 inhibited the expression of cysteine-rich protein 61 (CYR61), a proliferation related gene. From our research, CYR61 may partially hinder NDRG2-mediated inhibition of cell proliferation. Overexpression of NDRG2 resulted in accumulation of cells in the G1 phase, which was accompanied by upregulation of p21 and p27 and downregulation of CDK4 and cyclin D1. Taken together, these data indicate that NDRG2 inhibits the proliferation of neuroblastoma cells partially through suppression of CYR61. Our findings offer novel insights into the physiological roles of NDRG2 in neuroblastoma cell proliferation, and NDRG2 may prove to be effective candidate for the treatment of children with neuroblastoma.

Objective To investigate the effect of mechanical thrombectomy with Solitaire AB stent in the treatment of acute cerebral artery occlusion.Methods The clinical data of 96 patients with acute cerebral artery occlusion (onset time ＜ 6 hours)treated by mechanical thrombectomy with Solitaire AB stent in the department of neurosurgery of the fifth central hospital of Tianjin from Octobe 2010 to March 2012 were analyzed retrospectively.Results Thrombectomy with Solitaire stent was successful in 59 patients with complete revascularization.26 patients with partial stenosis after thrombectomy were treated with stenting and 6 patients were completed revascularized.11 patients were failed in thc trcatmcnt of thrombectomy.65 patients were completed revascularized and achieved TICI scored 3 in all of successful cases.20 patients achieved TICI scores 2b.Intracranial hemorrhage on follow-up CT was noted in 16.7％ (16 of 96) of patients.15 patients suffered slight hemorrhage and there was 1 moderate hemorrhage case.The National Institutes of Health Stroke Scale(NIHSS) score was 6.87 ± 4.56 at one week after procedure compared to 11.34 ± 5.48 before procedure.There was significant difference (P ＜ 0.05).The follow-up modified Rankin Scale (mRS) was less than 2 in 46 cases.Conclusions The application of Solitaire stent in acute stroke was safe and time-efficient,which could improve the recanalization rate,decrease or even avoid the application of thrombolytic drugs and reduce the rate of intracranial hemorrhage.

Objective To search for the targets of microRNA (miR)-7 in the epidermal growth factor receptor (EGFR) downstream pathway,and study the internal mechanism of glioma growth inhibition by miR-7.Methods After CHG5 glioma cells were transiently transfected with miR-7 sequence,reverse transcriptase quantitative PCR (RT-qPCR) method was used to detect the gene transfection.Methyl thiazol tetrazolium (MTT) assay was used to draw cell growth curves,Transwell assay to detect cell migration,and the soft agar colony formation assay to detect tumorigenicity.Western blotting was used to detect the expression of phosphatidylinositol 3 kinase (PI3K),Raf-1,Cyclin D1,p-protein kinase B (AKT) and pmitogen extracellular kinase 1/2 (p-MEK1/2).The TargetScan and Sanger softwares were used to co-predict the potential targets of miR-7.Luciferase experiments were used to test the relationship between miR-7 and PI3K or Raf-1.Results As compared with control and scramble groups,the ability of proliferation and migration,and clone of cells in miR-7 group were obviously declined (P ＜ 0.05).Western blotting results showed that the expression of EGFR downstream members was decreased.Luciferase experiments confirmed that both PI3K and Raf-1 were the direct targets of miR-7.Conclusion miR-7 can inhibit glioma growth by simultaneously regulating PI3K/ATK and Raf/MEK/ERK pathways both in EGFR downstream pathway.

It is generally believed that malignant gliomas never metastasize outside the central nervous system (CNS). However, the notion that oligodendrogliomas (OGDs) cells cannot spread outside CNS is being challenged. We described in detail the clinical story of one patient with anaplastic OGD, which metastasized to lymph nodes, bone marrowand bones Genetic analyses included detection of 1p and 19q chromosomal arms, methylation status of MGMT promoter, and PTEN exon mutations. A search of worldwide literature was conducted for reports of metastatic OGDs using NCBI-PubMed, with the keywords “extracranial”, “extraneural”, “oligodendroglioma”, “oligodendrogliomas”, “metastatic”, “metastasis”, and “metastases”, in different combinations. An open biopsy of the infiltrated bones in our patient revealed that malignant cells had replaced the patient’s marrow. Moreover, the diagnosis of multiple-organ metastases of anaplastic OGD was confirmed based on immunohistochemical staining. Genetic analyses showed that the tumors originated from previously resected brain lesions. None of the lesions had 1p and 19q deletions, but hypermethylation of MGMT promoter, and the G → A transversion at codon 234 of PTEN exon 2 were detected. Literatures review yielded 60 reports of metastatic OGDs from 1951 to the present, which with our patient makes 61 cases. Concerning these 61 patients, there were 110 infiltrated sites correlated closely with primary OGDs. The most frequent metastatic sites were bone and bone marrow (n = 47; 42.7%), lymph nodes (n = 22; 20.0%), liver (n = 7; 6.4%), scalp (n = 6; 5.5%), lung (n = 6; 5.5%), pleura (n = 4; 3.6%), chest wall (n = 3; 2.7%), iliopsoas muscle (n = 2; 1.8%), soft tissue (n = 2; 1.8%), and parotid gland (n = 2; 1.8%). Extracranial metastases in anaplastic OGD are very rare but they do occur; bone and bone marrow may be the most common sites. Detection of certain molecular markers such as deletion of 1p and 19q chromosomal arms, hypermethylation of MGMT promoter, and characteristic PTEN exon mutations may help differentiate subtypes which are more prone to extracranial metastases. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8749838611478560 .

Nonsteroidal anti-inflammatory drug (NSAID) activated gene-1 (NAG-1) is a divergent member of the transforming growth factor-beta (TGF-β) superfamily. NAG-1 plays remarkable multifunctional roles in controlling diverse physiological and pathological processes including cancer. Like other TGF-β family members, NAG-1 can play dual roles during cancer development and progression by negatively or positively modulating cancer cell behaviors. In glioblastoma brain tumors, NAG-1 appears to act as a tumor suppressor gene; however, the precise underlying mechanisms have not been well elucidated. In the present study, we discovered that overexpression of NAG-1 induced apoptosis in U87 MG, U118 MG, U251 MG, and T98G cell lines via the intrinsic mitochondrial pathway, but not in A172 and LN-229 cell lines. NAG-1 could induce the phosphorylation of PI3K/Akt and Smad2/3 in all six tested glioblastoma cell lines, except Smad3 phosphorylation in A172 and LN-229 cell lines. In fact, Smad3 expression and its phosphorylation were almost undetectable in A172 and LN-229 cells. The PI3K inhibitors promoted NAG-1-induced glioblastoma cell apoptosis, while siRNAs to Smad2 and Smad3 decreased the apoptosis rate. NAG-1 also stimulated the direct interaction between Akt and Smad3 in glioblastoma cells. Elevating the level of Smad3 restored the sensitivity to NAG-1-induced apoptosis in A172 and LN-229 cells. In conclusion, our results suggest that PI3K/Akt and Smad-dependent signaling pathways display opposing effects in NAG-1-induced glioblastoma cell apoptosis.

Common variants of multiple genes play a role in glioma onset. However, research related to astrocytoma, the most common primary brain neoplasm, is rare. In this study, we chose 21 tagging SNPs (tSNPs), previously reported to be associated with glioma risk in a Chinese case–control study from Xi’an, China, and identified their contributions to astrocytoma susceptibility. We found an association with astrocytoma susceptibility for two tSNPs (rs6010620 and rs2853676) in two different genes: regulator of telomere elongation helicase 1 (RTEL1) and telomerase reverse transcriptase (TERT), respectively. We confirmed our results using recessive, dominant, and additive models. In the recessive model, we found two tSNPs (rs2297440 and rs6010620) associated with increased astrocytoma risk. In the dominant model, we found that rs2853676 was associated with increased astrocytoma risk. In the additive model, all three tSNPs (rs2297440, rs2853676, and rs6010620) were associated with increased astrocytoma risk. Our results demonstrate, for the first time, the potential roles of RTEL1 and TERT in astrocytoma development.

Abstract As glioma ranks as the first most prevalent solid tumors in primary central nervous system, certain single-nucleotide polymorphisms (SNPs) may be related to increased glioma risk, and have implications in carcinogenesis. The present case–control study was carried out to elucidate how common variants contribute to glioma susceptibility. Ten candidate tagging SNPs (tSNPs) were selected from seven genes whose polymorphisms have been proven by classical literatures and reliable databases to be tended to relate with gliomas, and with the minor allele frequency (MAF) > 5% in the HapMap Asian population. The selected tSNPs were genotyped in 629 glioma patients and 645 controls from a Han Chinese population using the multiplexed SNP MassEXTEND assay calibrated. Two significant tSNPs in RTEL1 gene were observed to be associated with glioma risk (rs6010620, P = 0.0016, OR: 1.32, 95% CI: 1.11-1.56; rs2297440, P = 0.001, OR: 1.33, 95% CI: 1.12-1.58) by χ 2 test. It was identified the genotype “GG” of rs6010620 acted as the protective genotype for glioma (OR, 0.46; 95% CI, 0.31-0.7; P = 0.0002), while the genotype “CC” of rs2297440 as the protective genotype in glioma (OR, 0.47; 95% CI, 0.31-0.71; P = 0.0003). Furthermore, haplotype “GCT” in RTEL1 gene was found to be associated with risk of glioma (OR, 0.7; 95% CI, 0.57-0.86; Fisher’s P = 0.0005; Pearson’s P = 0.0005), and haplotype “ATT” was detected to be associated with risk of glioma (OR, 1.32; 95% CI, 1.12-1.57; Fisher’s P = 0.0013; Pearson’s P = 0.0013). Two single variants, the genotypes of “GG” of rs6010620 and “CC” of rs2297440 (rs6010620 and rs2297440) in the RTEL1 gene, together with two haplotypes of GCT and ATT, were identified to be associated with glioma development. And it might be used to evaluate the glioma development risks to screen the above RTEL1 tagging SNPs and haplotypes. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1993021136961998