| Title |
DMD genomic deletions characterize a subset of progressive/higher-grade meningiomas with poor outcome
|
|---|---|
| Published in |
Acta Neuropathologica, August 2018
|
| DOI | 10.1007/s00401-018-1899-7 |
| Pubmed ID | |
| Authors |
Tareq A. Juratli, Devin McCabe, Naema Nayyar, Erik A. Williams, Ian M. Silverman, Shilpa S. Tummala, Alexandria L. Fink, Aymen Baig, Maria Martinez-Lage, Martin K. Selig, Ivanna V. Bihun, Ganesh M. Shankar, Tristan Penson, Matthew Lastrapes, Dirk Daubner, Matthias Meinhardt, Silke Hennig, Alexander B. Kaplan, Shingo Fujio, Benjamin M. Kuter, Mia S. Bertalan, Julie J. Miller, Julie M. Batten, Heather A. Ely, Jason Christiansen, Gustavo B. Baretton, Anat O. Stemmer-Rachamimov, Sandro Santagata, Miguel N. Rivera, Fred G. Barker, Gabriele Schackert, Hiroaki Wakimoto, A. John Iafrate, Scott L. Carter, Daniel P. Cahill, Priscilla K. Brastianos |
| Abstract |
Progressive 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-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 ultimately 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)]. Given the known poor prognostic association of TERT alterations in these tumors, we also assessed for these events, 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, DMD alterations identify a subset of progressive/high-grade meningiomas with worse outcomes. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 2 | 29% |
| Germany | 1 | 14% |
| Unknown | 4 | 57% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 71% |
| Scientists | 1 | 14% |
| Practitioners (doctors, other healthcare professionals) | 1 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 52 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 13% |
| Student > Ph. D. Student | 7 | 13% |
| Student > Bachelor | 6 | 12% |
| Student > Doctoral Student | 4 | 8% |
| Professor | 3 | 6% |
| Other | 7 | 13% |
| Unknown | 18 | 35% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 12 | 23% |
| Medicine and Dentistry | 10 | 19% |
| Nursing and Health Professions | 2 | 4% |
| Immunology and Microbiology | 2 | 4% |
| Agricultural and Biological Sciences | 2 | 4% |
| Other | 2 | 4% |
| Unknown | 22 | 42% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 December 2020.
All research outputs
#4,295,759
of 25,378,162 outputs
Outputs from Acta Neuropathologica
#1,026
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Outputs of similar age
#77,424
of 343,928 outputs
Outputs of similar age from Acta Neuropathologica
#22
of 33 outputs
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