Mngi-37. Dmd Genomic Deletions Characterize a Subset of Progressive/higher-grade Meningiomas With Poor Outcome
Year: 2018
Type: conference-abstract
Abstract: Progressive meningiomas that have failed surgery and radiation have poor a 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 progressive/high-grade tumors, including matched primary and recurrent samples. We detected frequent alterations in genes residing on the X-chromosome, with somatic intragenic deletions of the dystrophin-encoding and muscular dystrophy-associated DMD gene as the most common alteration (n= 5, 20.8%), along with alterations of other known X-linked cancer-related genes KDM6A (n= 2, 8.3%), DDX3X, RBM10 and STAG2 (n= 1, 4.1% each). DMD inactivation (by genomic deletion or loss of protein expression) was detected in 17/53 progressive meningioma patients (32%). Importantly, patients with tumors harboring DMD 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)]. We also assessed for TERT alterations, which have a known poor prognostic association, and found seven patients with TERT promoter mutations and three with TERT rearrangements in this cohort (n= 10, 18.8%), including a recurrent novel RETREG1-TERT rearrangement that was present in two patients. In a multivariate model, DMD inactivation (p=0.033, HR=2.6, 95% CI 1.0–6.6) and TERT alterations (p= 0.005, HR= 3.8, 95% CI 1.5- 9.9) were mutually independent in predicting unfavorable outcomes. Thus, alterations of the mesodermal gene DMD identify a subset of progressive/high-grade meningiomas with worse outcomes.
Source: Neuro-Oncology
Authors: Tareq Juratli, Devin McCabe, Naema Nayyar, Erik Williams, Ian Silverman, Maria Martinez-Lage, Ganesh Shankar, Shilpa Tummala, Alexandria Fink, Julie Miller, Heather Ely, Jason Christiansen, Gabriele Schackert, Hiroaki Wakimoto, Miguel Rivera, John Iafrate, Scott Carter, Priscilla Brastianos, Daniel Cahill
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2900054135