Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma

Olar, Adriana; Wani, Khalida; Wilson, Charmaine D.; Zadeh, Gelareh; DeMonte, Franco; Jones, David; Pfister, Stefan M.; Sulman, Erik P.; Aldape, Kenneth

doi:10.1007/s00401-017-1678-x

Cited by 145 publications

(131 citation statements)

References 78 publications

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“…There are two limitations to our study. Several previous studies have explored DNA methylation profiling (14,(19)(20)(21), and it would be ideal to compare our classification system with that proposed by Sahm et al by performing RNA-seq and methylation profiling on the same samples (14). (Methylation and expression may (45) or may not (46) correlate.)…”

Section: Discussionmentioning

confidence: 99%

“…Bi et al found that grade III tumors are less likely to have TRAF7, KL4, AKT1, or SMO mutations but more likely to show genomic instability (copy number variation or CNV) (18). Vasudevan et al sought targetable pathways in high-grade meningiomas and found that high FOXM1 expression is associated with poor clinical outcomes (19); this is one of several studies showing that DNA methylation profiles have clinical relevance (14,(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors

Patel

Wan

Al‐Ouran

et al. 2019

Preprint

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Meningiomas account for one-third of all primary brain tumors. Although typically benign, about 20% of meningiomas are aggressive, and despite the rigor of the current histopathological classification system, there remains considerable uncertainty in predicting tumor behavior. Here, we analyzed 160 tumors from all three WHO grades (I-III) using clinical, gene expression and sequencing data. Unsupervised clustering analysis identified three molecular types (A, B, and C) that reliably predicted recurrence. These groups did not directly correlate with the WHO grading system, which would classify more than half of the tumors in the most aggressive molecular type as benign. Transcriptional and biochemical analyses revealed that aggressive meningiomas involve loss of the repressor function of the DREAM complex, which results in cell cycle activation; only tumors in this category tend to recur after full resection. These findings should improve our ability to predict recurrence and develop targeted treatments for these clinically challenging tumors. Significance StatementMeningiomas are the most common primary brain tumors. Although most of these tumors are benign, one-fifth will recur despite apparently complete resection. Several studies have demonstrated that genomic approaches can yield important insights into the biology of these tumors. We performed RNA sequencing and whole-exome sequencing of 160 tumors from 140 patients, which identified three distinct groups of meningioma that correlate with recurrence better than the current WHO grading system. Our analysis also revealed that the most aggressive type was characterized by loss of the repressive DREAM complex. These findings should improve prognostication for patients and lead to viable therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors

Patel

Wan

Al‐Ouran

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…A study by Olar et al. also found that DNA methylation analysis of meningiomas reliably identified patients with risk of tumor recurrence. Katz et al.…”

Section: Meningiomasmentioning

confidence: 94%

“…Approximately 20% meningioma patients have an aggressive clinical course with tumor recurrence and progressive disease (1,157,158). Extent of tumor resection and WHO grade are the most important clinical factors for predicting outcome (155,(159)(160)(161). However, currently the risk stratification of meningioma patients is imprecise as some patients with WHO grade I tumors experience early recurrence and an aggressive clinical course, whereas only 29-52% of WHO grade II tumors recur (1,161).…”

Section: Meningiomasmentioning

confidence: 99%

“…Extent of tumor resection and WHO grade are the most important clinical factors for predicting outcome (155,(159)(160)(161). However, currently the risk stratification of meningioma patients is imprecise as some patients with WHO grade I tumors experience early recurrence and an aggressive clinical course, whereas only 29-52% of WHO grade II tumors recur (1,161). Mutation in the NF2 gene and loss of chromosome 22 are the most frequent genetic alteration in meningiomas (1).…”

Section: Meningiomasmentioning

confidence: 99%

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Biomarkers in tumors of the central nervous system – a review

Scheie

Kufaishi

Broholm

et al. 2019

APMIS

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Until recently, diagnostics of brain tumors were almost solely based on morphology and immunohistochemical stainings for relatively unspecific lineage markers. Although certain molecular markers have been known for longer than a decade (combined loss of chromosome 1p and 19q in oligodendrogliomas), molecular biomarkers were not included in the WHO scheme until 2016. Now, the classification of diffuse gliomas rests on an integration of morphology and molecular results. Also, for many other central nervous system tumor entities, specific diagnostic, prognostic and predictive biomarkers have been detected and continue to emerge. Previously, we considered brain tumors with similar histology to represent a single disease entity. We now realize that histologically identical tumors might show alterations in different molecular pathways, and often represent separate diseases with different natural history and response to treatment. Hence, knowledge about specific biomarkers is of great importance for individualized treatment and follow‐up. In this paper we review the biomarkers that we currently use in the diagnostic work‐up of brain tumors.

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Incidence and survival of benign, borderline, and malignant meningioma patients in the United States from 2004 to 2018

Cao

Yan

et al. 2022

Intl Journal of Cancer

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Meningioma is the most common primary central nervous system tumor, and its incidence is increasing. A systematic epidemiological and clinical analysis is required to better estimate its public health impact and understand its prognostic factors. Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2018 for all types of meningiomas without an age restriction.Age-adjusted incidence rates (IRs) and 95% confidence intervals were estimated according to sex, age, race, ethnicity, and tumor location. Kaplan-Meier analysis and multivariate Cox proportional hazard models were used to analyze the overall survival (OS). The competing risk regression model of Fine-Gray was used to analyze cause-specific survival. Data from a total of 109 660 meningioma patients were analyzed. A majority of patients were older than 60 years, and only 0.41% of patients were 0-19 years. The meningioma IRs were higher in females, Black, and non-Hispanic patients than in males, White, and Hispanic patients, respectively, and IRs increased with age. The ratio of IRs for females to males was 2.1 and also increased with age, peaking at 3.6 in the 45-49-year-old group. Older and male patients with all types of meningiomas, Black patients with benign and borderline meningiomas, and patients with larger borderline and malignant meningiomas showed poorer prognosis. For all meningioma types, surgical resection improved survival. The reported incidence rates and survival trends covered all demographics and subtypes of meningiomas. Older age, male sex, Black race, and tumor size may be important prognostic factors for meningioma cases, and tumor resection can substantially improve survival among meningioma patients.

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Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma

Cited by 145 publications

References 78 publications

Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors

Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors

Biomarkers in tumors of the central nervous system – a review

Incidence and survival of benign, borderline, and malignant meningioma patients in the United States from 2004 to 2018

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