title: High incidence of activating TERT promoter mutations in meningiomas undergoing malignant progression.
abstract: Meningiomas are common central nervous system tumors. The World Health Organization (WHO) defines three grades, predictive of the risk of recurrence. These tumors can relapse frequently and sometimes undergo malignant transformation. Maintenance of telomere length is a key process in malignant progression, and mutations in TERT promoter have recently been identified in various types of cancer. We sequenced the TERT promoter in 85 meningiomas from 73 patients. We found a high incidence of TERT promoter mutations in patients with meningiomas undergoing malignant histological progression (28%, n = 5/18 patients). In this subset of patients with histological progression, TERT promoter mutations were found in both the lowest and the highest grade tumors, and in both NF2-mutated and nonmutated samples. In contrast, one mutation was identified in 35 meningiomas without recurrence or progression, belonging to various histological grades. This sample was an aggressive meningioma in a patient who died shortly after surgery. Interestingly, tumors showing relapse without histological progression were not mutated for TERT promoter (n = 20). Finally, TERT promoter mutations were associated with a marked increase in TERT expression. Thus, TERT promoter mutations are pivotal genetic alterations involved in malignant progression of meningiomas and could be used as a biomarker to identify meningiomas at risk of malignant transformation.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Department of Neurosurgery, Hôpital Beaujon, Clichy, France; INSERM, Génomique Fonctionnelle des Tumeurs Solides, IUH, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Goutagny
authors.forename: Jean C
authors.initials: JC
authors.lastname: Nault
authors.forename: Maxime
authors.initials: M
authors.lastname: Mallet
authors.forename: Dominique
authors.initials: D
authors.lastname: Henin
authors.forename: Jessica Z
authors.initials: JZ
authors.lastname: Rossi
authors.forename: Michel
authors.initials: M
authors.lastname: Kalamarides
mesh_terms: D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: TERT promoter; malignant progression; meningioma; neurofibromatosis type 2