TERT rearrangements to identify a subset of aggressive meningiomas.

e14028Background: Although a significant proportion of aggressive meningiomas acquire TERT promoter (TERTp) mutations which drive TERT overexpression during progression, alternative mechanisms of telomere maintenance in meningioma are broadly unknown. TERT activating rearrangements are common in some aggressive cancers and associated with poor outcome. We sought to assess TERT rearrangements in a large cohort of patients with progressive meningiomas. Methods: We determined the frequency of TERT mRNA overexpression in 126 temporally- and regionally-distinct specimens from 55 WHO grades II/III meningioma patients using reverse-transcriptase PCR. Subsequently, RNA sequencing was performed in samples with TERT overexpression to detect rearrangements. Additionally, the TERTp region was sequenced in all patients to assess hotspot mutations. Results: We identified 9 samples from 3 patients (5.4%) with highly amplified TERT mRNA expression. RNA sequencing of these samples revealed a novel fusion RETREG1-TERT that...