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Researchers at Baylor College of Medicine and Washington University School of Medicine, St. Louis have identified clinical and genetic predictors of multiply recurrent meningiomas (MRMs), a most aggressive form of this common brain tumor. Published in Science Advances, the study opens new opportunities for future development of potential biomarkers and therapeutic agents for these challenging tumors.

"Although meningiomas are often effectively treated with surgery and radiation, in about 20% of cases these tumors behave aggressively and recur. A smaller subset of these resist treatment and recur multiple times," said co-corresponding author Dr. Akash J. Patel, associate professor of neurosurgery and member of the Dan L Duncan Comprehensive Cancer Center at Baylor.

"We wanted to find out if meningiomas that come back multiple times and require multiple treatments are different at the molecular level from brain tumors that don't come back," said co-corresponding author Dr. Albert H. Kim, August A. Busch Jr. Professor of Neurosurgery and director of the Brain Tumor Center at Washington University School of Medicine. "Knowing which meningiomas will come back again and again will fundamentally change how we treat them from the very beginning."

The team studied the tumors of 1,186 patients with primary meningiomas. Thirty-one of these primary tumors went on to be MRMs. The researchers compared clinical and genetic characteristics of MRM with those of non-recurrent meningiomas (NRM).

"We found that, compared to NMR, MRM are more numerous, larger and more common in men than in women," Patel said.

The researchers analyzed the chromosomes of the tumors and found that MRMs have greater chromosomal instability and loss than non-aggressive meningiomas. "It has been well established that chromosomal instability is present in many human cancers and that increased instability has been associated with more aggressive cancers," Patel said. "Our finding that greater chromosomal instability is associated with MRMs, a more aggressive form of meningiomas, is an important point to study in the future."

In addition, the researchers found increased DNA methylation in MRM's genomes, an indication that the expression of certain genes is different in these tumors. "We discovered that the expression of gene EDNRB is reduced in MRM tumor cells," Patel said. "When we knocked down this gene in meningioma cells in the lab, the cells proliferated more. Taken together, this first clinical and molecular investigation of MRMs provides a deeper understanding of these highly aggressive tumors."

"This information will teach us how to fight them better with precision medicine and lays the foundation for predicting at the time of the first surgery which meningiomas will most likely recur repeatedly," Kim said.
Drs. Sangami Pugazenthi and Bhuvic Patel at Washington University and Dr. Collin W. English at Baylor are co-first authors of the work.

Other contributors to this work include William A. Leidig, Kyle P. McGeehan, Colin R. McCornack, Shinghei Mok, Markus Anzaldua-Campos, Shervin Hosseingholi Nouri, Kaleigh Roberts, Ajay Chatrath, A. Basit Khan, Ron Gadot, Hiroko Yano, Tiemo J. Klisch, Akdes S. Harmanci and Albert Kim.

This work was supported by the Alvin J. Siteman Cancer Research Fund GF0010218, the Duesenberg Research Fund, Washington University School of Medicine Dean's Medical Student Research Fellowship for the MD5 Yearlong Research Program, 2023 NREF Medical Student Summer Research Fellowship, NINDS - K08NS102474 and the Roderick D. MacDonald Fund.