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Redefining medulloblastoma

New research from one of our funded grants gives much needed insight into group 3 and 4 medulloblastoma

New research from one of our funded grants, co-funded with Children with Cancer and Great Ormond Street Hospital Children’s Charity, gives much needed insight into group 3 and 4 medulloblastoma

This work published in the scientific journal Acta Neuropathologica, is the result of collaborative effort between respected medulloblastoma researchers from the UK, USA, Canada and Germany.

Using samples from over 1500 medulloblastoma tumours, they’ve been able to refine group 3 and 4 tumours into eight distinct types.

Medulloblastoma is the most common high grade brain tumour found in children, accounting for 15-20% of all childhood brain tumours.

Since 2012 researchers have agreed that this tumour can be divided into four subgroups based on clinical, genetic, and demographic differences.

The four medulloblastoma subgroups are called: WNT, SHH, group 3, and group 4, with 65% of medulloblastomas diagnosed as group 3 or group 4 tumours.

All children who are diagnosed with group 3 and group 4 medulloblastoma are currently assigned the same risk level and so are given the same intense treatment.

In 2017 three high-profile research groups each published results that showed group 3 and group 4 medulloblastoma should be further divided into different types.

The problem was that these teams analysed the samples in different ways, resulting in a different number of types for each analysis.

In this new paper all three of these research teams have joined forces to provide us with a consensus on the new “types”.

How did they do it?

The three research teams provided their colleagues with access to all the tumour samples that they used in their individual studies. They then assessed all 1501 samples using statistics as well as biological methods.

The three teams had each used different statistical methods to group the tumour samples. These groups were based on similarities and differences that the researchers found between the tumours.

For this consensus study, instead of choosing only one statistical analysis at the start, the researchers used methods from all three individual studies on each sample to find the method that worked best.

Once the statistical analysis had been completed, the researchers agreed on five new types. However, they still needed to look further into the biology of the tumours.

The researchers then started looking at changes in chromosomes, or parts of chromosomes, which are structures that organise DNA in all of our cells.

Through this investigation the teams were able to further refine their classification into eight groups, which they gave names “Types I-VIII”.

Key findings

One of the key findings from this work was the observation that each of the eight new types were seen to be more commonly diagnosed in children of a specific age.

For example, type IV is more common in infants (under 3 years old), while type VIII is more often diagnosed in children about 10 years old.

Another interesting finding showed that three of the new types (II, III and V) were found to have an increased risk of tumour progression.

Type VIII was also highlighted, as children with this type often had late relapses (more than 5 years after diagnosis), which were, at times, fatal.

This research also highlights the importance of knowing how group 3 and 4 medulloblastomas start. That is why we are funding research that looks into where these tumours.

What does it mean?

This research means that we are one step closer to more tailored clinical care for children with groups 3 and 4 medulloblastoma.

Specifically, the researchers plan to look at whether some children might benefit from different treatments.

This means that the tumour could be treated more aggressively where appropriate (types II, III or V), or that the child could be spared unnecessary treatments and their associated side effects (type IV).

While these results won’t immediately impact treatments in the clinic, they provide a more detailed road map on the journey to precision medicine.