A review of epigenetic and gene expression alterations associated with intracranial meningiomas

He, Shuhan; Pham, Martin H.; Pease, Matthew; Zada, Gabriel; Giannotta, Steven L.; Wang, Kai; Mack, William J.

doi:10.3171/2013.10.focus13360

Cited by 56 publications

(52 citation statements)

References 90 publications

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“…They are typically associated with brain invasion and recurrence, and the overall 10‐year survival rate is only 14.2% (Fathi & Roelcke ; He et al . ). Meningiomas have very broad spectrum of clinical characteristics and there is a considerable variability in the biological behaviour within each of the tumour grades.…”

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confidence: 97%

“…Unfortunately, there are also 3% of anaplastic meningiomas (WHO Grade III) that are aggressive and will exhibit malignant behaviour. They are typically associated with brain invasion and recurrence, and the overall 10-year survival rate is only 14.2% (Fathi & Roelcke 2013;He et al 2013). Meningiomas have very broad spectrum of clinical characteristics and there is a considerable…”

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confidence: 99%

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Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

Pećina‐Šlaus

Kafka

Vladušić

et al. 2016

Int J Experimental Path

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Crosstalk between Wnt and p53 signalling pathways in cancer has long been suggested. Therefore in this study we have investigated the involvement of these pathways in meningiomas by analysing their main effector molecules, beta-catenin and p53. Cellular expression of p53 and beta-catenin proteins and genetic changes in TP53 were analysed by immunohistochemistry, PCR/RFLP and direct sequencing of TP53 exon 4. All the findings were analysed statistically. Our analysis showed that 47.5% of the 59 meningiomas demonstrated loss of expression of p53 protein. Moderate and strong p53 expression in the nuclei was observed in 8.5% and 6.8% of meningiomas respectively. Gross deletion of TP53 gene was observed in one meningioma, but nucleotide alterations were observed in 35.7% of meningiomas. In contrast, beta-catenin, the main Wnt signalling molecule, was upregulated in 71.2%, while strong expression was observed in 28.8% of meningiomas. The concomitant expressions of p53 and beta-catenin were investigated in the same patients. In the analysed meningiomas, the levels of the two proteins were significantly negatively correlated (P = 0.002). This indicates that meningiomas with lost p53 upregulate beta-catenin and activate Wnt signalling. Besides showing the reciprocal relationship between proteins, we also showed that the expression of p53 was significantly (P = 0.021) associated with higher meningioma grades (II and III), while beta-catenin upregulation was not associated with malignancy grades. Additionally, women exhibited significantly higher values of p53 loss when compared to males (P = 0.005). Our findings provide novel information about p53 involvement in meningeal brain tumours and reveal the complex relationship between Wnt and p53 signalling, they suggest an important role for beta-catenin in these tumours.

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confidence: 97%

mentioning

confidence: 99%

Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

Pećina‐Šlaus

Kafka

Vladušić

et al. 2016

Int J Experimental Path

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“…The vast majority of meningiomas are benign, while grade III meningiomas exhibit a higher rate of recurrence and death compared with grade I and II tumors4. Despite total surgical resection, a small segment of meningiomas do sometimes recur, which often leads to reoperation and an increased risk of morbidity and mortality56. Thus, novel molecular biomarkers that can facilitate early detection, progression monitoring, and clinical prediction to improve patient outcomes is particularly important.…”

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confidence: 99%

A serum 6-miRNA panel as a novel non-invasive biomarker for meningioma

Zhi

Shao

et al. 2016

Sci Rep

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Circulating microRNAs (miRNAs) hold great promise as novel clinically blood-based biomarkers for cancer diagnosis and prognosis. However, little is known about their impact in meningioma. The TLDA assay was performed as an initial survey to determine the serum miRNA expression profile in two pooled samples from 20 pre-operative meningiomas and 20 matched healthy controls. Selected candidate miRNAs were subsequently validated individually in another 210 patients and 210 healthy controls from two independent cohorts by qRT-PCR. The serum levels of miR-106a-5p, miR-219-5p, miR-375, and miR-409-3p were significantly increased, whereas the serum levels of miR-197 and miR-224 were markedly decreased. The area under the ROC curve (AUC) for the six combined miRNAs was 0.778. The 4 increased miRNAs were significantly decreased, while the 2 decreased miRNAs were significantly increased after tumor removal. Furthermore, the expression levels of miR-224 were associated with sex, and the expression levels of miR-219-5p were positively associated with the clinical stages of meningioma. Finally, the high expression of miR-409-3p and low expression of miR-224 were significantly correlated with higher recurrence rates. The present study revealed that the panel of 6 serum miRNA may have the potential to be used clinically as an auxiliary tool for meningioma patients.

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“…Some earlier studies described TP73 hypermethylation as the mechanism involved in the suppression of its expression 29 , but other studies claim that TP73 expression could be higher in anaplastic meningiomas, but lower because of hypermethylation in low-grade meningiomas 33 . In the present case, TP73 was not methylated in any tumour.…”

Section: Discussionmentioning

confidence: 99%

Molecular Progression in Unusual Recurrent Non-Pediatric Intracranial Clear Cell Meningioma

et al. 2017

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We report a case of a recurrent clear cell meningioma (ccm) in the frontal lobe of the brain of a 67-year-old man. The patient developed three recurrences: at 3, 10, and 12 years after his initial surgery. Histopathology observations revealed a grade 2 ccm with positivity for vimentin and epithelial membrane antigen. Expression of E-cadherin was positive only in the primary tumour and in the first available recurrence. Fluorescence in situ hybridization analyses demonstrated 1p and 14q deletions within the last recurrence. Multiplex ligation-dependent probe amplification studies revealed a heterozygous partial NF2 gene deletion, which progressed to total loss in the last recurrence. The last recurrence showed homozygous deletions in CDKN2A and CDKN2B. The RASSF1 gene was hypermethylated during tumour evolution.In this report, we show the genetic alterations of a primary ccm and its recurrences to elucidate their relationships with the changes involved in the progression of this rare neoplasm.

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A review of epigenetic and gene expression alterations associated with intracranial meningiomas

Cited by 56 publications

References 90 publications

Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

A serum 6-miRNA panel as a novel non-invasive biomarker for meningioma

Molecular Progression in Unusual Recurrent Non-Pediatric Intracranial Clear Cell Meningioma

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