Human TERT Promoter Mutations in Atypical and Anaplastic Meningiomas

Mellai, Marta; Prandini, Omar Porrini; Mustaccia, Aurora; Fogazzi, Valentina; Allesina, Marta; Krengli, Marco; Boldorini, Renzo

doi:10.3390/diagnostics11091624

Cited by 4 publications

(3 citation statements)

References 37 publications

(77 reference statements)

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“…In addition to the genes mentioned previously herein, a 2018 study showed that mutations in the promoter of telomerase reverse transcriptase ( TERTp ) enhance the degree of malignancy of meningiomas and lead to poor prognosis ( 51 ). Other studies have corroborated that TERTp mutations predict poor survival in progressive/high-grade meningiomas ( 33 , 52 , 53 ). Telomere maintenance is a marker of tumor formation, and most tumors express telomerase to prevent telomere shortening ( 52 ).…”

Section: Cell Proliferationmentioning

confidence: 80%

Potential Molecular Mechanisms of Recurrent and Progressive Meningiomas: A Review of the Latest Literature

Peng

Yuan

et al. 2022

Front. Oncol.

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Meningiomas, the most frequent primary intracranial tumors of the central nervous system in adults, originate from the meninges and meningeal spaces. Surgical resection and adjuvant radiation are considered the preferred treatment options. Although most meningiomas are benign and slow-growing, some patients suffer from tumor recurrence and disease progression, eventually resulting in poorer clinical outcomes, including malignant transformation and death. It is thus crucial to identify these “high-risk” tumors early; this requires an in-depth understanding of the molecular and genetic alterations, thereby providing a theoretical foundation for establishing personalized and precise treatment in the future. Here, we review the most up-to-date knowledge of the cellular biological alterations involved in the progression of meningiomas, including cell proliferation, neo-angiogenesis, inhibition of apoptosis, and immunogenicity. Focused genetic alterations, including chromosomal abnormalities and DNA methylation patterns, are summarized and discussed in detail. We also present latest therapeutic targets and clinical trials for meningiomas' treatment. A further understanding of cellular biological and genetic alterations will provide new prospects for the accurate screening and treatment of recurrent and progressive meningiomas.

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Section: Cell Proliferationmentioning

confidence: 80%

Potential Molecular Mechanisms of Recurrent and Progressive Meningiomas: A Review of the Latest Literature

Peng

Yuan

et al. 2022

Front. Oncol.

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“…Mutations in SETD2, TP53, TERT promoter and NF2 were not consistently present across recurrent tumours. Although Mellai et al reported the association of the TERT promoter mutations to histologic grade [49]. TERT promoter mutations have not been found to be significantly associated with the recently described molecular subtypes [15,50].…”

Section: Discussionmentioning

confidence: 95%

Somatic mutation landscape in a cohort of meningiomas that have undergone grade progression

et al. 2023

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Background A subset of meningiomas progress in histopathological grade but drivers of progression are poorly understood. We aimed to identify somatic mutations and copy number alterations (CNAs) associated with grade progression in a unique matched tumour dataset. Methods Utilising a prospective database, we identified 10 patients with meningiomas that had undergone grade progression and for whom matched pre- and post-progression tissue (n = 50 samples) was available for targeted next-generation sequencing. Results Mutations in NF2 were identified in 4/10 patients, of these 94% were non-skull base tumours. In one patient, three different NF2 mutations were identified in four tumours. NF2 mutated tumours showed large-scale CNAs, with highly recurrent losses in 1p, 10, 22q, and frequent CNAs on chromosomes 2, 3 and 4. There was a correlation between grade and CNAs in two patients. Two patients with tumours without detected NF2 mutations showed a combination of loss and high gain on chromosome 17q. Mutations in SETD2, TP53, TERT promoter and NF2 were not uniform across recurrent tumours, however did not correspond with the onset of grade progression. Conclusion Meningiomas that progress in grade generally have a mutational profile already detectable in the pre-progressed tumour, suggesting an aggressive phenotype. CNA profiling shows frequent alterations in NF2 mutated tumours compared to non NF2 mutated tumours. The pattern of CNAs may be associated with grade progression in a subset of cases.

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“…These findings highlight the role of TERT promoter alteration as a possible prognostic marker of recurrence and survival. Several studies have shown that TERT promoter mutation in meningiomas is associated with worse prognosis and shorter overall survival independent of WHO grade [42][43][44][45].…”

Section: Other Rarer Mutationsmentioning

confidence: 99%

Discovering the Molecular Landscape of Meningioma: The Struggle to Find New Therapeutic Targets

et al. 2021

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Meningiomas are the most common primary CNS tumors. They are usually benign but can present aggressive behavior in about 20% of cases. The genetic landscape of meningioma is characterized by the presence (in about 60% of cases) or absence of NF2 mutation. Low-grade meningiomas can also present other genetic alterations, particularly affecting SMO, TRAF7, KLF4 AKT1 and PI3KCA. In higher grade meningiomas, mutations of TERT promoter and deletion of CDKN2A/B seem to have a prognostic value. Furthermore, other genetic alterations have been identified, such as BAP1, DMD and PBRM1. Different subgroups of DNA methylation appear to be correlated with prognosis. In this review, we explored the genetic landscape of meningiomas and the possible therapeutic implications.

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Human TERT Promoter Mutations in Atypical and Anaplastic Meningiomas

Cited by 4 publications

References 37 publications

Potential Molecular Mechanisms of Recurrent and Progressive Meningiomas: A Review of the Latest Literature

Potential Molecular Mechanisms of Recurrent and Progressive Meningiomas: A Review of the Latest Literature

Somatic mutation landscape in a cohort of meningiomas that have undergone grade progression

Discovering the Molecular Landscape of Meningioma: The Struggle to Find New Therapeutic Targets

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