DNA methylation subtype and H3K27Me3 status of a case of clear-cell meningioma of the lateral sphenoid wing

AbstractClear cell meningioma represents an uncommon variant of meningioma that typically affects children and young adults. Although an enrichment of loss-of-function mutations in the SMARCE1 gene has been reported for this subtype, comprehensive molecular investigations are lacking. Here we describe a molecularly distinct subset of tumors (n = 31), initially identified through genome-wide DNA methylation screening among a cohort of 3093 meningiomas, of which most were diagnosed histologically as clear cell meningioma. This cohort was further supplemented by an additional 11 histologically diagnosed clear cell meningiomas for analysis (n = 42). Targeted DNA sequencing revealed SMARCE1 mutations in 33/34 analyzed samples, accompanied by a nuclear loss of expression determined via immunohistochemistry and a decreased SMARCE1 transcript expression in the tumor cells. Analysis of time to progression or recurrence of patients within the clear cell meningioma group (n = 14) in comparison to those with meningioma WHO grade 2 (n = 220) revealed a similar outcome and support the assignment of WHO grade 2 to these tumors. Our findings indicate the existence of a highly distinct epigenetic signature of clear cell meningiomas, separate from all other variants of meningiomas, with recurrent mutations in the SMARCE1 gene. This suggests that these tumors may arise from a different precursor cell population than the broad spectrum of the other meningioma subtypes.

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LAT, HOXD3 and NFE2L3 identified as novel DNA methylation-driven genes and prognostic markers in human clear cell renal cell carcinoma by integrative bioinformatics approaches

Journal of Cancer ◽

10.7150/jca.35641 ◽

2019 ◽

Vol 10 (26) ◽

pp. 6726-6737 ◽

Cited By ~ 4

Author(s):

Jie Wang ◽

Hu Zhao ◽

Huiyue Dong ◽

Ling Zhu ◽

Shuiliang Wang ◽

...

Keyword(s):

Dna Methylation ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Prognostic Markers ◽

Clear Cell ◽

Cell Renal Cell Carcinoma

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Downregulation of lncRNA ZNF582-AS1 due to DNA hypermethylation promotes clear cell renal cell carcinoma growth and metastasis by regulating the N(6)-methyladenosine modification of MT-RNR1

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01889-8 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Wuping Yang ◽

Kenan Zhang ◽

Lei Li ◽

Yawei Xu ◽

Kaifang Ma ◽

...

Keyword(s):

Dna Methylation ◽

Renal Cell Carcinoma ◽

Protein Expression ◽

Cell Carcinoma ◽

Clinical Significance ◽

Renal Cell ◽

Clear Cell ◽

Expression Level ◽

Cell Renal Cell Carcinoma ◽

Qrt Pcr

Abstract Background Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear. Methods Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level. Results ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression. Conclusions This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.

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Identification of DNA methylation signatures associated with poor outcome in lower-risk Stage, Size, Grade and Necrosis (SSIGN) score clear cell renal cell cancer

Clinical Epigenetics ◽

10.1186/s13148-020-00998-z ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Louis Y. El Khoury ◽

Shuang Fu ◽

Ryan A. Hlady ◽

Ryan T. Wagner ◽

Liguo Wang ◽

...

Keyword(s):

Dna Methylation ◽

Renal Cell ◽

Lower Risk ◽

Clear Cell ◽

Cell Cancer ◽

Low Risk ◽

Cell Renal Cell Carcinoma ◽

A Genome ◽

Size Grade ◽

Prognostic Power

Abstract Background Despite using prognostic algorithms and standard surveillance guidelines, 17% of patients initially diagnosed with low risk clear cell renal cell carcinoma (ccRCC) ultimately relapse and die of recurrent disease, indicating additional molecular parameters are needed for improved prognosis. Results To address the gap in ccRCC prognostication in the lower risk population, we performed a genome-wide analysis for methylation signatures capable of distinguishing recurrent and non-recurrent ccRCCs within the subgroup classified as ‘low risk’ by the Mayo Clinic Stage, Size, Grade, and Necrosis score (SSIGN 0–3). This approach revealed that recurrent patients have globally hypermethylated tumors and differ in methylation significantly at 5929 CpGs. Differentially methylated CpGs (DMCpGs) were enriched in regulatory regions and genes modulating cell growth and invasion. A subset of DMCpGs stratified low SSIGN groups into high and low risk of recurrence in independent data sets, indicating that DNA methylation enhances the prognostic power of the SSIGN score. Conclusions This study reports a global DNA hypermethylation in tumors of recurrent ccRCC patients. Furthermore, DMCpGs were capable of discriminating between aggressive and less aggressive tumors, in addition to SSIGN score. Therefore, DNA methylation presents itself as a potentially strong biomarker to further improve prognostic power in patients with low risk SSIGN score (0–3).

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An unusual case of clear cell meningioma

Journal of Cancer Research and Therapeutics ◽

10.4103/0973-1482.59902 ◽

2009 ◽

Vol 5 (4) ◽

pp. 324 ◽

Cited By ~ 2

Author(s):

Prabal Deb ◽

SubramanyaG.S Datta

Keyword(s):

Unusual Case ◽

Clear Cell ◽

Clear Cell Meningioma

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Intracranial clear cell meningioma in two children with blood relations: two case reports and literature review

Child s Nervous System ◽

10.1007/s00381-012-1840-7 ◽

2012 ◽

Vol 28 (12) ◽

pp. 2143-2151 ◽

Cited By ~ 10

Author(s):

Zhiqi Li ◽

Yi Zhang ◽

Enming Wang ◽

Zhiqiu Wang ◽

Wengang Li ◽

...

Keyword(s):

Literature Review ◽

Clear Cell ◽

Case Reports ◽

Clear Cell Meningioma

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Molecular progression in unusual recurrent non-pediatric intracranial clear cell meningioma

Current Oncology ◽

10.3747/co.24.3509 ◽

2017 ◽

Vol 24 (3) ◽

pp. 244

Author(s):

B. Domingo-Arrué ◽

R. Gil-Benso ◽

J. Megías ◽

L. Navarro ◽

T. San-Miguel ◽

...

Keyword(s):

Clear Cell ◽

Primary Tumour ◽

Antigen Expression ◽

Genetic Alterations ◽

Clear Cell Meningioma ◽

Initial Surgery ◽

Homozygous Deletions ◽

The Brain ◽

Dependent Probe

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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