Unravelling the network of brain tumour genetics

The genetic map, developed by researchers at the UCL Queen Square Institute of Neurology, is analogous to a map of the London Underground – where different genetic features responsible for driving brain tumours are like stations connected by tracks.

Mapping the genetic changes should enable more accurate prediction of survival than standard diagnostic approaches.

The wide diversity of genetic changes that enable tumour cells to grow has made brain tumours – a common cause of death and disability worldwide – remarkably difficult to treat. Identifying effective treatments requires an understanding of the variable – and highly individual – relation between tumour genetics, patient outcomes, and disease mechanisms. Crucially, because this diversity is due to the interaction between multiple genetic changes in tumour development, it is ideally captured as a network.

Just as the shortest path from a given station to another is best found by analysing the whole network of stations and tracks, the shortest path from normal to abnormal cells in an individual patient is best found by identifying the whole network of possible genetic changes leading to brain tumour development.

In the largest study of its kind, applying state-of-the-art network analysis to tumour genetic data from 4023 patients with brain tumours, drawn over 14 years across 12 countries, researchers at the UCL Queen Square Institute of Neurology have revealed a new map of the network of individual tumour genetic changes in patients with glioma: amongst the hardest brain tumours to treat.

The research is published in the journal Brain.

Derived from data routinely collected during clinical care, the map is demonstrated to enable more accurate prediction of individual patient survival than the ‘gold-standard’ diagnostic’ labels adopted by the World Health Organization. Since the approach does not require new tests, it offers an efficient path to improved, more personalised care without any increase to healthcare costs.

Lead author, Dr James Ruffle (Clinical Research Fellow (Brain Entry Fellowship), Brain Repair & Rehabilitation, UCL Queen Square Institute of Neurology, says: "The treatment of brain tumours is in desperate need of innovation: outcomes have hardly changed over the past 30 years.

A critical step is gaining an understanding of tumour genetic diversity, which we show here to be accessible, but only to data and mathematical models of great size and complexity. A radical change of approach is needed, and we now have the computational tools to bring it into reality.”

The teams’ work was funded by the Wellcome Trust, the Medical Research Council, and the UCLH Biomedical Research Centre.

Links

• James K Ruffle and others, Brain tumour genetic network signatures of survival, Brain, 2023;, awad199, https://doi.org/10.1093/brain/awad199
• Dr James Ruffle's academic profile

Source: NIHR UCLH BRC

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• Credit: peterschreiber.media on iStock