A surreal DNA labyrinth with a red strand leading to a darkened cityscape, symbolizing DMD's role in aggressive meningioma.

Meningioma's Genetic Puzzle: How DMD Deletions Impact Progression and Treatment

Avery Sinclair in Health & Wellness December 2025 • 5 min read.

"Decoding a Novel Link Between a Muscle-Related Gene and Meningioma Severity"

Progressive meningiomas pose a significant challenge in neuro-oncology. These tumors, which have resisted both surgery and radiation, leave patients with limited treatment options and a bleak prognosis. Although meningiomas generally affect more women, aggressive forms disproportionately impact men. Understanding the unique molecular drivers behind these resilient tumors is crucial for developing targeted therapies.

A recent study published in Acta Neuropathologica sheds light on this complex problem. Researchers conducted a comprehensive molecular analysis of 169 meningioma samples from 53 patients with progressive or high-grade tumors. This included examining both initial and recurrent tumor samples to track genetic changes over time.

The findings reveal a surprising connection: deletions in the DMD gene, well-known for causing Duchenne muscular dystrophy, are strongly linked to poorer outcomes in a subset of aggressive meningiomas. This discovery, along with insights into TERT gene alterations, opens new avenues for understanding and potentially treating these challenging tumors.

DMD Deletions: Unmasking the Culprit in Aggressive Meningiomas

A surreal DNA labyrinth with a red strand leading to a darkened cityscape, symbolizing DMD's role in aggressive meningioma.

The research team's initial exome sequencing of 24 meningioma samples revealed frequent alterations in genes residing on the X chromosome. Among these, DMD (dystrophin) stood out. Somatic intragenic deletions of DMD were the most common alteration, found in approximately 21% of the initial cohort. Further investigation revealed alterations in other X-linked cancer-related genes such as KDM6A, DDX3X, RBM10, and STAG2, though less frequently.

Importantly, the study expanded its scope, ultimately detecting DMD inactivation (through genomic deletion or loss of protein expression) in a significant 32% of the 53 progressive meningioma patients. The impact on survival was profound. Patients whose tumors harbored DMD inactivation experienced significantly shorter overall survival compared to those with wild-type DMD. Specifically, median overall survival was 5.1 years (95% CI 1.3-9.0) for those with the inactivation versus much higher for wild-type DMD.

DMD encodes dystrophin, a protein crucial for muscle function but also involved in cell structure and signaling.
DMD deletions were more common in aggressive meningiomas compared to less severe forms.
The study suggests that loss of dystrophin may disrupt cellular architecture, contributing to tumor progression.

To confirm that DMD deletions were not simply a marker of general genomic instability, the researchers conducted several control analyses. They found that DMD deletions clustered in specific regions of the gene and were not associated with other fragile sites in the genome. This specificity strengthens the argument that DMD inactivation plays a direct role in promoting aggressive meningioma behavior.

A New Path Forward: Targeting DMD and TERT for Improved Meningioma Therapy

The study didn't stop with DMD. Recognizing the established role of TERT alterations in aggressive meningiomas, the researchers also investigated these events. They identified seven patients with TERT promoter mutations and three with TERT rearrangements, including a recurrent and novel RETREG1-TERT rearrangement present in two patients. This dual focus revealed that DMD inactivation and TERT alterations act independently to predict unfavorable outcomes.

Multivariate modeling confirmed this independence: 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) each significantly predicted shorter survival, regardless of the other's presence. This means that future treatment strategies may need to consider both DMD and TERT status to effectively target aggressive meningiomas.

These findings provide a crucial step forward in understanding the genetic underpinnings of aggressive meningiomas. By identifying DMD deletions as a key driver of poor outcomes, the study opens the door for developing novel therapeutic strategies. Furthermore, the independent roles of DMD and TERT suggest that combination therapies targeting both pathways may be necessary to significantly improve patient survival. Future clinical trials should incorporate DMD and TERT stratification to ensure that the most effective treatments are delivered to those who need them most.

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This article is based on research published under:

DOI-LINK: 10.1007/s00401-018-1899-7, Alternate LINK

Title: Dmd Genomic Deletions Characterize A Subset Of Progressive/Higher-Grade Meningiomas With Poor Outcome

Subject: Cellular and Molecular Neuroscience

Journal: Acta Neuropathologica

Publisher: Springer Science and Business Media LLC

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

Published: 2018-08-19

Everything You Need To Know

What specific gene alteration was found to be linked to poorer outcomes in aggressive meningiomas?

The discovery centers on the *DMD* gene, which, when inactivated through deletions, is strongly linked to poorer outcomes in aggressive meningiomas. This gene, typically associated with Duchenne muscular dystrophy, plays a crucial role in cell structure and signaling. The research indicated that *DMD* deletions were more common in aggressive meningiomas compared to less severe forms. Patients with *DMD* inactivation experienced significantly shorter overall survival, highlighting the gene's impact on disease progression.

Why is it important to understand the genetic drivers behind aggressive meningiomas?

Aggressive meningiomas present a significant challenge due to their resistance to conventional treatments like surgery and radiation, leaving patients with limited options. The research emphasizes the need for targeted therapies by identifying genetic drivers. The study points towards *DMD* inactivation and *TERT* alterations as independent predictors of unfavorable outcomes. These findings highlight that these genetic alterations are crucial in understanding and potentially treating these challenging tumors.

What role does the DMD gene play, and what happens when it is altered?

The *DMD* gene is known for causing Duchenne muscular dystrophy, a muscle-related condition. In the context of meningiomas, *DMD* encodes dystrophin, a protein involved in both muscle function and cell structure. Deletions in *DMD* lead to the loss of this protein. Loss of *DMD* has significant implications, including shorter overall survival and potentially disrupting cellular architecture, thus contributing to more aggressive tumor behavior.

Besides DMD, what other gene alterations were investigated, and what were the findings?

The study found that alterations in *TERT* (telomerase reverse transcriptase) are also significant. Specifically, seven patients showed *TERT* promoter mutations and three with *TERT* rearrangements, including a novel *RETREG1-TERT* rearrangement. The combination of *DMD* inactivation and *TERT* alterations independently predicted unfavorable outcomes. This dual focus underscores the importance of understanding the complete genetic profile to improve treatment strategies for aggressive meningiomas.

What are the potential implications of this research for the treatment of aggressive meningiomas?

The implications of these findings are significant for developing new treatment strategies. By identifying *DMD* inactivation as a key driver of aggressive behavior, researchers can now focus on developing targeted therapies that specifically address this genetic alteration. The study opens new avenues for understanding and potentially treating these challenging tumors, with the aim of improving patient outcomes and survival rates. This might include developing drugs that target dystrophin pathways or interfere with the mechanisms by which *DMD* inactivation promotes tumor growth. The researchers can now develop the specific treatment for each patient based on their genetic profile, for example, those with *TERT* alterations.