Rethinking How to Grade Brain Cancer

The ability to predict how a tumour will behave is a critical part of planning treatment. The grade of a tumour—a category assigned based on how aggressive the cancer is expected to be—can help. However, sometimes these categories do not reliably capture the behaviour of a tumour, which can make predicting patient outcomes and planning appropriate treatment a challenge.  

Clinicians have long faced these issues when grading meningiomas, tumours that come from the membranes that surround the brain and spinal cord (called the meninges). In a new study from UHN’s Princess Margaret Cancer Centre (PM), researchers may have found a way to resolve this issue and make grading meningiomas significantly more reliable. The team, led by Drs. Gelareh Zadeh and Farshad Nassiri, an Affiliate Scientist and Scientist, respectively, at PM, found that meningiomas with certain chromosomal changes called copy number alterations (CNAs)—in particular a 1p loss (a loss of the first half of chromosome 1) or 1q gain (a copy gain in the latter half of chromosome 1)— behave more aggressively than their grade would predict. As a result, these tumours may not be receiving the best treatment, negatively impacting patient outcomes.

“Improving care for patients begins with ensuring that we accurately evaluate their tumour and predict how it will behave,” remarks Dr. Nassiri. “We’ve been studying genetic changes in meningiomas and how they impact tumour biology for years,” notes Dr. Alexander Landry, one of the first authors of the study, “but translating these discoveries has proved to be a challenge thus far.” “Our work offers a way to improve meningioma grading in clinical practice today without requiring tests that are impractical in most cancer care settings because they’re prohibitively expensive or need specialized technology and staff not available everywhere,” adds Dr. Zadeh.

This work highlights the critical need to improve the WHO grading system for CNS tumours like meningiomas, such as by incorporating genetic features like CNAs into grading criteria. Because meningiomas are one of the most common types of brain cancer in adults, rectifying the inconsistency in the current system could significantly improve care for a large population of patients with a challenging diagnosis and offer more patients a better chance at life after meningioma. 

Drs. Alexander Landry and Justin Wang, the first authors on this study, are Graduate Researchers at the Princess Margaret Cancer Centre (PM), as well as Doctor of Philosophy candidates and neurosurgery residents at the University of Toronto. 

Drs. Gelareh Zadeh and Farshad Nassiri are the senior authors on this study. Dr. Zadeh is an Affiliate Scientist at PM, a neurosurgeon at UHN’s Toronto Western Hospital (TWH), a Professor in the Faculty of Medicine at the University of Toronto, and the Chair of Neurosurgery at the Mayo Clinic. Dr. Nassiri is a Scientist at PM, a neurosurgeon at UHN in the Sprott Department of Surgery and a neurosurgeon at TWH, and an Assistant Professor in the Faculty of Medicine at the University of Toronto. 

This work was supported by the International Consortium of Meningiomas, Brain Tumour Charity UK, CCS, Canadian Institutes of Health Research, and the Princess Margaret Cancer Foundation. 

Landry AP‡, Wang JZ‡, Patil V, Liu J, Gui C, Ellenbogen Y, Ajisebutu A, Yefet L, Wei Q, Singh O, Sosa J, Mansouri S, Cohen-Gadol AA, Tabatabai G, Tatagiba M, Behling F, Barnholtz-Sloan JS, Sloan AE, Chotai S, Chambless LB, Mansouri A, Makarenko S, Yip S, Ehret F, Capper D, Tsang DS, Moliterno J, Gunel M, Wesseling P, Sahm F, Aldape K, Gao A, Zadeh G#, Nassiri F#. Chromosome 1p Loss and 1q Gain for Grading Meningioma. JAMA Oncol. 2025 April 3. doi: 10.1001/jamaoncol.2025.0329. 

‡Contributed equally as first authors. 

#Contributed equally as senior authors.