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Childhood brain tumours are actually many different diseases

Study findings could lead to better targeted treatments

Jo Carlowe

Friday, 29 September 2017

Deadly childhood brain tumours are at least 10 different diseases that should each be diagnosed and treated based on their specific genetic faults.

The finding is part of a major new study,* published this week in Cancer Cell, and has implications for treatment, since personalising care for each type of brain tumour is likely to be much more effective than grouping them all together as one.

A team at The Institute of Cancer Research, London, found stark differences among children's 'high grade' brain tumours, or gliomas, and that they could be split into at least 10 different cancers.

Some types should be far more treatable than others using drugs under development or already on the market, state the scientists.

The study is the world's largest of these aggressive childhood brain cancers and should lead to more accurate diagnostic tests to ensure each child receives the best possible treatment.

Many of the children had mutations in their tumours that can be targeted by existing drugs approved for adult cancers, demonstrating the benefit of testing children for genetic mutations in their tumours at the point of diagnosis.

Researchers gathered genetic data from 910 cases from 20 previously published analyses and 157 new cases, from children or young adults up to the age of 30 with high-grade glioblastoma or diffuse intrinsic pontine glioma (DIPG).

The tumours could be split into different subtypes based on different characteristics, such as age at diagnosis, area of the brain, the number of genetic mutations and errors in key genes that drive the disease.

One of the striking findings from the study was that while some children's tumours were driven by a single genetic error in which two genes were fused together, others had tens of thousands of genetic errors - among the highest number of mutations in any human cancer.

Tumours with mutations in a gene called BRAF were found to be much less aggressive than some of the other cancers, and actually shouldn't be classified as 'high grade' at all, state the authors. These tumours could be susceptible to several adult cancer drugs that target BRAF mutations.

Scientists at the Institute of Cancer Research, found mutations in common cancer genes such as PDGFRA, KIT, MYCN, EGFR, CDK6, and genes involved in DNA repair - all of which can be targeted by existing drugs.

They also uncovered numerous new potential therapeutic targets within each subtype, such as the gene TOP3A - a gene involved in DNA replication - in tumours with a specific type of histone mutation called H3.3K27M.

Three of the subtypes were distinguished by the presence or absence of different mutations in genes that produce histones. Although there are currently no drugs that can target histone mutations, there are some in development and the presence or absence of these mutations gave clues about how aggressive the cancer is, and could point to future approaches to treatment.

Study leader Professor Chris Jones, Professor of childhood brain tumour biology at The Institute of Cancer Research, London, said: "Our study uncovered a wealth of new information about children's brain cancers. We found that tumours that have historically been lumped together under one diagnosis are in fact comprised of many, remarkably different, diseases.

"Treating cancer based only on what we see down the microscope simply isn't good enough any more. We need to start thinking about these as completely different cancers and diagnosing and treating them based on their genetic faults. It's exciting that several types look like they could be clearly treatable using either existing drugs on the market or other treatments under development.

"We worked with colleagues across the world to gather enough data on these rare cancers to understand better what makes them so aggressive, and what mutations occur that might make them susceptible to different treatments.”

The data produced by this study is now considered the definitive dataset on these cancers, and will be made available on a public data portal so the research community can use it to develop new tests and treatments.


* Mackay A, Burford A, Carvalho D, et al. Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma. Cancer Cell, published online 28 September 2017. DOI: 10.1016/j.ccell.2017.08.017

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