DMD genomic deletions characterize a subset of progressive/higher-grade meningiomas with poor outcome

AbstractProgressive meningiomas that have failed surgery and radiation have a poor prognosis and no standard therapy. While meningiomas are more common in females overall, progressive meningiomas are enriched in males. We performed a comprehensive molecular characterization of 169 meningiomas from 53 patients with progressive/high-grade tumors, including matched primary and recurrent samples. Exome sequencing in an initial cohort (n = 24) detected frequent alterations in genes residing on the X chromosome, with somatic intragenic deletions of the dystrophin-encoding and muscular dystrophy-associatedDMD gene as the most common alteration (n = 5, 20.8%), along with alterations of other known X-linked cancer-related genesKDM6A (n  =2, 8.3%),DDX3X, RBM10 andSTAG2 (n = 1, 4.1% each).DMD inactivation (by genomic deletion or loss of protein expression) was ultimately detected in 17/53 progressive meningioma patients (32%). Importantly, patients with tumors harboringDMD inactivation had a shorter overall survival (OS) than their wild-type counterparts [5.1  years (95% CI 1.3–9.0) vs. median not reached (95% CI 2.9–not reached,p = 0.006)]. Given the known poor prognostic association ofTERT alterations in these tumors, we also assessed for these events, and found seven patients withTERT promoter mutations and three withTERT rearrangements in this cohort (n = 10, 18.8%), including a recurrent novelRETREG1–TERT rearrangement that was present in two patients. ...
Source: Acta Neuropathologica - Category: Neurology Source Type: research