Alterations of telomere length in human brain tumors

Kheirollahi, Majid; Mehrazin, Masoud; Kamalian, Naser; Mehdipour, Parvin

doi:10.1007/s12032-010-9506-3

Cited by 16 publications

(10 citation statements)

References 45 publications

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“…Common germline variants in key telomere biology genes, RTEL1 and TERT, are associated with glioma risk [7-10]. Several studies have found a connection between telomerase levels, telomere heterogeneity, TERT promoter mutations and ALT in somatic glioma tissues and provide further evidence for a biological connection [14] [15-20]. A growing number of studies suggest that short germline RTL is a risk factor for certain cancers, including bladder, esophageal, gastric, head and neck, ovarian, renal and overall incident cancer[1].…”

Section: Discussionmentioning

confidence: 99%

“…Telomere length heterogeneity appears to be present in brain tumors. Some brain tumors appear to up-regulate telomerase whereas others maintain telomere length through the alternative lengthening of telomere pathway (ALT) [15-20]. The ALT pathway may play a role in specific subsets of glioma with mutations in Alpha Thalassemia/Mental Retardation X-linked (ATRX) and/or isocitrate dehydrogenase genes (IDH1) [18].…”

Section: Introductionmentioning

confidence: 99%

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Telomere length and risk of glioma

Walcott

Rajaraman

Gadalla

et al. 2013

Cancer Epidemiology

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Background Telomere length in blood or buccal cell DNA has been associated with risk of various cancers. Glioma can be a highly malignant brain tumor and has few known risk factors. Genetic variants in or near RTEL1 and TERT, key components of telomere biology, are associated with glioma risk. Therefore, we evaluated the association between relative telomere length (RTL) and glioma in a prospective study. Materials and Methods We performed a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. RTL was determined by quantitative PCR on blood or buccal cell DNA obtained at least two years prior to diagnosis from 101 individuals with glioma cases. Healthy controls (n=198) were matched to cases (2:1) on age, gender, smoking status, calendar year, and DNA source. Conditional logistic regression was used to investigate the association between RTL and glioma. Results As expected, RTL declined with increasing age in both cases and controls. There was no statistically significant association between RTL and glioma overall. An analysis stratified by gender suggested that short RTL (1st tertile) in males was associated with glioma (odds ratio, [OR] = 2.29, 95% confidence interval [CI] 1.02-5.11); this association was not observed for females (OR=0.41, 95% CI 0.14-1.17). Conclusions This prospective study did not identify significant associations between RTL and glioma risk, but there may be gender-specific differences. Larger, prospective studies are needed to evaluate these findings.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Telomere length and risk of glioma

Walcott

Rajaraman

Gadalla

et al. 2013

Cancer Epidemiology

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“…Given the critical role of MCPH1 in modulation of telomere repeat length, we analyzed the correlation between the MCPH1 promoter methylation and telomere length of each patients through southern blotting (Kheirollahi et al 2010). Significant association was found between MCPH1 promoter methylation and brain tumor's grade and stage.…”

Section: How Does Mcph1 Gene Behave In Brain Tumors?mentioning

confidence: 99%

Epigenetics Territory and Cancer

Mehdipour¹

2015

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“…The TL of all the patients, which was previously assayed [27], was statistically analyzed with ATM promoter methylation and clinicopathological features. In addition, status of TL was confirmed by Q-FISH which showed either severe lack or low intensity of signals (Fig.…”

Section: Telomere Lengthmentioning

confidence: 99%

Linking ATM Promoter Methylation to Cell Cycle Protein Expression in Brain Tumor Patients: Cellular Molecular Triangle Correlation in ATM Territory

et al. 2014

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Ataxia telangiectasia mutated (ATM) is a key gene in DNA double-strand break (DSB), and therefore, most of its disabling genetic alterations play an important initiative role in many types of cancer. However, the exact role of ATM gene and its epigenetic alterations, especially promoter methylation in different grades of brain tumors, remains elusive. The current study was conducted to query possible correlations among methylation statue of ATM gene, ATM/ retinoblastoma (RB) protein expression, D1853N ATM polymorphism, telomere length (TL), and clinicopathological characteristics of various types of brain tumors. Isolated DNA from 30 fresh tissues was extracted from different types of brain tumors and two brain tissues from deceased normal healthy individuals. DNAs were treated with bisulfate sodium using DNA modification kit (Qiagen). Methylation-specific polymerase chain reaction (MSP-PCR) was implicated to determine the methylation status of treated DNA templates confirmed by promoter sequencing. Besides, the ATM and RB protein levels were determined by immunofluorescence (IF) assay using monoclonal mouse antihuman against ATM, P53, and RB proteins. To achieve an interactive correlation, the methylation data were statistically analyzed by considering TL and D1853N ATM polymorphism. More than 73% of the brain tumors were methylated in ATM gene promoter. There was strong correlation between ATM promoter methylation and its protein expression (p < 0.001). As a triangle, meaningful correlation was also found between methylated ATM promoter and ATM protein expression with D1853N ATM polymorphism (p = 0.01). ATM protein expression was not in line with RB protein expression while it was found to be significantly correlated with ATM promoter methylation (p = 0.01). There was significant correlation between TL neither with ATM promoter methylation nor with ATM protein expression nor with D1853N polymorphism. However, TL has shown strong correlation with patient's age and tumor grade (p = 0.01). Given the important role of cell cycle checkpoint proteins as well as RB and ATM in TL and cancer evolution, further assessment is warranted to shed more light on the pathway linking the telomere instability to tumor progression. High ATM methylation rate in brain tumor patients could open a new avenue toward early screening and cancer therapy.

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Alterations of telomere length in human brain tumors

Cited by 16 publications

References 45 publications

Telomere length and risk of glioma

Telomere length and risk of glioma

Epigenetics Territory and Cancer

Linking ATM Promoter Methylation to Cell Cycle Protein Expression in Brain Tumor Patients: Cellular Molecular Triangle Correlation in ATM Territory

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