Early warning sign of aggressive brain tumours could help tailor treatment

Meningiomas are the most common primary brain tumour in adults.

New research suggests that testing for Telomerase Reverse Transcriptase (TERT) expression could improve understanding of which patients are at risk of faster disease progression. This is important knowledge that could help inform treatment decisions. 

The study, part-funded by us, was led by researchers at the University of Toronto. They recently published their findings in the Lancet Oncology.

What is the TERT gene?

The TERT gene is responsible for making a type of protein called telomerase, which helps repair and rebuild telomeres. These are pieces of DNA that protect the ends of chromosomes like the plastic tips at the ends of shoelaces that keep them from unravelling.  

In healthy cells, telomeres shorten each time the cell divides. But cells with mutated TERT genes activate telomerase, allowing them to rebuild the telomeres and divide indefinitely. Previous research in other tumours and cancers has found that this encourages tumour growth. 

About meningioma

Meningiomas begin in the set of three membranes just inside the skull (called the meninges), which cover and protect the brain and spinal cord.

Under World Health Organisation criteria, meningiomas can be classed as grades 1, 2 or 3. They are usually low grade, but some grow quicker than others and may come back after treatment.

People who are diagnosed with a grade 1 meningioma are often put on active monitoring treatment (also known as ‘watch and wait’). Surgery and radiotherapy may be offered later if needed. Grade 2 and 3 types usually have surgery, then radiotherapy.

What did the research find?

This study analysed over 1,200 meningioma samples from Canada, Germany and the USA. Around a third (32%) of them expressed TERT, while less than 3% (2.9%) had a TERT promoter mutation.

This is the first study of its kind to show that TERT expression – even without a mutation in the TERT gene – can predict earlier disease progression.

We found that high TERT expression is strongly linked to faster disease progression, and it was about 10 times more common than mutations in the gene. This makes it a promising biomarker for identifying patients who may be at greater risk of recurrent disease."

Dr Gelareh Zadeh, neurosurgeon and senior author

Significantly, the researchers found that TERT-positive tumours behaved as if they were a grade worse than their official diagnosis. For example, a grade 1 tumour that expressed TERT acted more like a grade 2.

By identifying high-risk meningiomas, we can offer treatment that better aligns with how the tumour behaves. Our ongoing research looks at the biology of TERT and how to bring this biomarker into the everyday clinical workflow."

Chloe Gui, neurosurgery resident and lead author

Welcoming the research

Israr Jan-Parker, a former senior lecturer, now brain tumour advocate, from Southampton, was diagnosed with a petroclival meningioma in May 2022, after multiple visits to medical professionals. She welcomed the research:

“As someone living with a meningioma that couldn’t be fully removed, I am filled with the uncertainty of “when will it grow?”

“Knowing a test could pinpoint a more aggressive tumour earlier offers genuine hope.  It means future patients like myself could receive more tailored, timely treatment instead of an anxious ‘watch and wait’. This is the progress we are all fighting for.”

What does our expert think?

Find out more about Dr Zadeh’s meningioma research

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