Targeting clinically challenging meningiomas

Fast facts

• Official title: Deciphering the genetic and epigenetic landscape of clinically aggressive meningiomas
• Lead researcher: Dr Gelareh Zadeh
• Where: University Health Network, Toronto, Canada
• When: October 2017 – September 2022
• Cost: £1.5 million over five years
• Research type: Adult, Meningioma (High Grade), Clinical/ Academic
• Grant round: Quest for cures

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What is it? 

Identifying changes in DNA 

Dr Zadeh aims to identify key molecules within a cell that start, as well as maintain, the growth of high grade meningiomas.

The team will analyse tumour samples from 500 patients around the world to identify changes in DNA. They’ll also analyse how changes to the the way DNA is folded influences the way the DNA ‘code’ is used. This analysis will help to identify and target the changes associated with fuelling the aggressive nature of high grade meningiomas.

Connecting genetic changes to clinical behaviour

In addition to tumour samples, the researchers will also collect information on a person’s quality of life, including persistent symptoms such as fatigue. This information will be used to establish a clinical registry of symptoms, which will be correlated to the impact of the tumour to everyday life. This will help capture both genetic and quality of life information and help propel progress for those affected.

Why is it important? 

Almost a quarter of all primary brain tumours in adults are meningiomas. As many as 90% are considered low grade, but a small subset are high grade. These are referred to as ‘clinically aggressive meningiomas’, or ‘CAMs’. Beyond surgery and radiation therapy, treatment options for CAMs are limited, making it essential to understand the biology of these high grade meningiomas so we can pick up the pace towards a cure for those affected.

Who will it help? 

This research will help identify changes associated with CAMs to help improve diagnosis and identify drug targets to treat this tumour type. This project will also help halve the harm caused by brain tumours by gathering information on a person’s quality of life.

This research hopes to drive change for people with clinically aggressive meningiomas, for whom treatment options are currently limited.

Milestones 

Achieved 

• The researchers have collected 490 tumour samples from people with CAMs and are in the process of analysing the changes to DNA and its structure and have sequenced the protein-coding regions of DNA in 450 meningioma samples. This allowed the researchers to identify important mutations that make the tumour more aggressive.
• The team has also determined the DNA methylation profiles of 140 meningiomas and used this data to build a tool that can predict the risk of tumour regrowth after surgery
• Research by Zadeh’s team has indicated that a loss of a specific, or marker, called ‘H3K27 trimethylation’ could help predict how meningioma tumours might behave. Their results suggest that loss of this marker is associated with higher grade tumours, and faster regrowth after surgery in meningioma patients.
• The UK arm of the project, led by Michael Jenkinson, has established two new ‘core outcome sets’ for meningioma in their COSMIC study. These define the minimum outcomes that should be measured and reported across all meningioma clinical trials.
• By consulting patients, healthcare professionals, carers and charities, the team have developed a set of outcomes, including things like as tumour growth, overall quality of life, and progression-free survival.
• This means that separate studies can measure the same set of outcomes in patients, to allow better comparison between different clinical trials, and ensure better quality research into meningiomas.