Today sees the publication of a major research study that improves our understanding of a type of childhood brain cancer, called diffuse intrinsic pontine glioma, or DIPG.
The study, published in the journal
Nature Genetics, links together this type of glioma with an extremely rare developmental disorder called fibrodysplasia ossificans progressiva, or FOP, known colloquially as Stone Man Syndrome.
The finding was unexpected, surprising and intriguing to the researchers who made the discovery, and could ultimately help lead to new treatments for children with DIPG.
The research was led by Dr Chris Jones here at The Institute of Cancer Research in London and showed that mutations to a particular gene called
ACVR1 are found in a sub-set – around a quarter – of children with DIPG.
The surprising detail is that mutations in
ACVR1 are the cause of the developmental disorder FOP, in which the muscles, tendons and ligaments of affected individuals gradually turn to bone. Two other studies that Dr Jones and his team also contributed to, published simultaneously in the same journal and led by other international experts, bear out the link between the two diseases.
Quite how mutations in the same gene can have such different effects in different situations is a mystery. In children with FOP, mutations to
ACVR1 are found in every cell in their body. In DIPG, the mutations emerge sporadically in cells in the brain, apparently playing an important role in the growth and spread of the cancer.
The implications
The discovery is not only scientifically surprising but also important because of the landmark it represents in our understanding of DIPG. Diagnosed in 20-30 children in the UK each year and emerging in the brain stem, it is currently incurable: for a child, a diagnosis of DIPG means they will live for an average of 9-12 months.
The
ACVR1 gene encodes a type of protein called a kinase. Kinases play varied and important roles within our cells and are very important in cancer, while kinase inhibitors have become increasingly important in cancer treatment. This means that researchers might be able to draw on decades of expertise in developing kinase inhibitors to potentially help those children with DIPG who carry this specific genetic mutation. It’s even possible that potential drugs being developed for children with FOP could also help treat children with DIPG.
The role of families – and the future
This ICR study relied on the help of the families of children with DIPG who were treated in Paris, who volunteered for biopsies to be taken from the brain stem for use in research. Some of the families who gave samples had made the trip to Paris from other countries, including the UK, because biopsies are not generally taken from children with DIPG by surgeons unless they are enrolled on a clinical trial to test new treatments. Unfortunately, there are currently no open trials for DIPG in the UK – but the passion of families affected by DIPG to drive forward research was the driver behind this new understanding of the disease. One family affected personally by DIPG were the focus of
our recent appeal to raise funds for childhood cancer.
Applying the results of today’s studies to children in the clinic is still some way off, and more research will be needed before new drugs are available for children with DIPG. Eventually, the hope is that doctors could use an ACVR1-targeting drug in these children. As Dr Jones’s study has shown, children whose tumours carry this mutation seem to represent a distinct subgroup of DIPG, and it will increase the importance of taking tumour biopsies to identify which patients will benefit most from such an approach. The new discovery brings that hope a step closer, but there are no clinical trials of new treatments yet planned.
Find out more Please view our video about the new study – and you can see Chris and Katy thanking the funders of the study (Cancer Research UK, Abbie’s Army, the Lyla Nsouli Foundation and the Stavros Niarchos Foundation) in their
personal thank you video note.
The study leading to the publication of the paper also recently won a
prestigious award at the world’s leading annual conference of brain tumour experts, beating nearly 1,000 other submissions. Katy Taylor – a PhD student in Chris Jones’ team – picked up the award on behalf of the ICR and the other study co-authors at the conference.
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