Researchers have pinpointed both clinical and genetic indicators for multiply recurrent meningiomas (MRMs), which represent a particularly aggressive type of this prevalent brain tumor.
A team from Baylor College of Medicine and Washington University School of Medicine in St. Louis has discovered clinical and genetic indicators for multiply recurrent meningiomas (MRMs), an especially aggressive variant of this common brain tumor. The findings, published in Science Advances, pave the way for the development of potential biomarkers and treatment options for these challenging tumors.
“While many meningiomas can be managed effectively through surgery and radiation, approximately 20% of these tumors show aggressive behavior and return. A smaller number resist treatment and reappear multiple times,” explained Dr. Akash J. Patel, a co-corresponding author and associate professor of neurosurgery at Baylor’s Dan L Duncan Comprehensive Cancer Center.
“We aimed to determine whether meningiomas that frequently recur and necessitate numerous treatments differ at the molecular level from those that do not recur,” said Dr. Albert H. Kim, another co-corresponding author and the August A. Busch Jr. Professor of Neurosurgery at Washington University School of Medicine. “Understanding which meningiomas are likely to recur can significantly influence our treatment approach from the outset.”
The researchers examined the tumors from 1,186 patients suffering from primary meningiomas, of which 31 evolved into MRMs. They compared the clinical and genetic traits of MRMs with those of non-recurrent meningiomas (NRMs).
“Our analysis showed that MRMs tend to be more frequent, larger, and occur more often in men than in women compared to NRMs,” Patel noted.
The team also explored the chromosomes of the tumors and identified that MRMs exhibit greater chromosomal instability and loss compared to their non-aggressive counterparts. “Chromosomal instability is a well-known characteristic in various human cancers, and heightened instability is often linked to more aggressive forms of the disease,” Patel remarked. “This association between increased chromosomal instability and MRMs, the more aggressive meningiomas, is a key area for future research.”
Moreover, the researchers discovered heightened DNA methylation within the genomes of MRMs, suggesting variations in gene expression in these tumors. “We found that the expression of the gene EDNRB is diminished in cells from MRM tumors,” Patel explained. “When we inhibited this gene in meningioma cells in laboratory settings, those cells proliferated more. This initial clinical and molecular insight into MRMs enhances our comprehension of these highly aggressive tumors.”
“These insights could lead us to improve treatment strategies through precision medicine, and they establish a basis for predicting at the time of initial surgery which meningiomas are most likely to recur repeatedly,” Kim added.
Drs. Sangami Pugazenthi and Bhuvic Patel from Washington University, along with Dr. Collin W. English from Baylor, are co-first authors of the study.
Other contributors 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, and Akdes S. Harmanci.
This research received support from the Alvin J. Siteman Cancer Research Fund GF0010218, the Duesenberg Research Fund, the Washington University School of Medicine Dean’s Medical Student Research Fellowship for the MD5 Yearlong Research Program, the 2023 NREF Medical Student Summer Research Fellowship, NINDS — K08NS102474, and the Roderick D. MacDonald Fund.
