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Meningioma Grading beyond Histopathology: Relevance of Epigenetic and Genetic Features to Predict Clinical Outcome

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Simple Summary Meningiomas are common tumors of the central nervous system. The grading system established by the World Health Organization has recently included pTERT mutations and CDKN2A/B homozygous deletions as… Click to show full abstract

Simple Summary Meningiomas are common tumors of the central nervous system. The grading system established by the World Health Organization has recently included pTERT mutations and CDKN2A/B homozygous deletions as criteria for grade 3, owing to their close association with increased recurrence risk. However, these alterations identify only a part of meningiomas that are devoid of histopathological malignancy and are prone to recurrence. This review summarizes the most recent knowledge on the molecular landscape of meningiomas, according to which these tumors can be classified into three main groups, showing distinct clinical outcomes and epigenetic, genetic, transcriptomic, and proteomic features. There is some evidence that these groups can be distinguished in routine practice using specific immunostaining and may likely be treated with different and targeted approaches. Abstract Meningiomas are common tumors of the central nervous system. The grading system established by the World Health Organization (WHO) has recently included pTERT mutations and CDKN2A/B homozygous deletions as criteria for grade 3, owing to their association with increased recurrence risk. However, these alterations identify only a portion of meningiomas that are devoid of histopathological malignancy and are prone to recurrence. Over the last few years, the integration of epigenetic, genetic, transcriptomic, and proteomic profiling has led to the identification of three main groups of meningiomas with distinct clinical outcomes and peculiar genetic features. Meningiomas in the first group have the best prognosis, are distinguished by the lack of NF2 alterations and chromosomal instability, and may be responsive to cytotoxic drugs. Meningiomas in the second group have an intermediate prognosis and are characterized by NF2 alterations, mild chromosomal instability, and enrichment in immune cells. Meningiomas in the third group had the worst prognosis, displayed NF2 alterations coupled with high chromosomal instability, and were resistant to cytotoxic treatment. Classification into these three groups predicts the recurrence risk of meningiomas more accurately than WHO grading and could be applicable in routine practice, owing to the possibility of distinguishing the different groups by specific immunostaining.

Keywords: system; epigenetic genetic; meningiomas; recurrence; genetic features; histopathology

Journal Title: Cancers
Year Published: 2023

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