High Incidence of Activating TERT Promoter Mutations in Meningiomas Undergoing Malignant Progression. (23rd December 2013)

• Record Type: Journal Article
• Authors: Goutagny, Stéphane; Nault, Jean C.; Mallet, Maxime; Henin, Dominique; Rossi, Jessica Z.; Kalamarides, Michel
• Is Part Of: Brain pathology. Volume 24:Number 2(2014:Mar.)
• Page Start: 184
• Page End: 189
• Publication Date: 2013-12-23
• Subjects: Nervous system -- Diseases -- Periodicals; Brain -- Diseases -- Periodicals; Neurology -- Periodicals; Brain Diseases -- Periodicals; Cerveau -- Maladies -- Périodiques; Système nerveux -- Maladies -- Périodiques; Neurologie -- Périodiques; 616.805
• DOI: 10.1111/bpa.12110
• Languages: English
• ISSNs: 1015-6305

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>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 <italic>TERT</italic> promoter have recently been identified in various types of cancer. We sequenced the <italic>TERT</italic> promoter in 85 meningiomas from 73 patients. We found a high incidence of <italic>TERT</italic> promoter mutations in patients with meningiomas undergoing malignant histological progression (28%, n = 5/18 patients). In this subset of patients with histological progression, <italic>TERT</italic> promoter mutations were found in both the lowest and the highest grade tumors, and in both <italic>NF</italic><italic>2</italic>‐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 <italic>TERT</italic> promoter (n = 20). Finally, <italic>TERT</italic> promoter mutations were associated with a marked increase in <italic>TERT</italic> expression. Thus, <italic>TERT</italic> 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.</p> </abstract>