Identifying the causes of childhood brain tumours

Dr Katherine Karakoula is part of this vital team which has successfully identified a handful of genes that trigger ependymomas in children.

Ependymomas are the third most frequent kind of childhood tumour, with only half the children affected surviving for five years after they are diagnosed,’ explains Dr Tracy Warr in her lab at the Institute of Neurology in central London. With three children of her own, Dr Warr fully understands the anguish of parents whose children have been diagnosed with brain tumours.

In earlier research, she and her colleagues had linked ependymomas to DNA changes on two chromosomes – 1 and 22. This was a good start but ‘within these two areas, there were thousands of genes, so we needed to find out which ones might be involved,’ she explains.

By looking at samples from 53 tumours, Tracy found that on chromosome 22, two genes were implicated. The first, called chibby, was switched off or deleted in six out of ten tumours. ‘What’s exciting is that in half the cases, the gene was still there. It had been switched off by an effect called hyper-methylation but treatments might be developed which can switch it back on. We know that this gene is involved in suppressing growth, so when it is off it may be unable to stop tumours growing,’ says Tracy. A second gene on chromosome 22, called rac2, had been deleted in a third of children where the tumour tended to recur. ‘This gene seems to be involved in the development of the neural network in the brain, so in children under two it could be exerting more of an influence than in older people,’ suspects Tracy.

On chromosome 1, three genes are clustered together in an area associated with growth promotion, so perhaps they are driving the growth of the tumour. A fourth gene, TPR, is also implicated and this closely associated with hard-to-kill tumours. All these genes were over-expressed – there were many copies – so this may indicate that over-expression needs to be controlled.

Dr Warr plans to test her findings to confirm which genes need targeting.

Now, Tracy plans to test her findings with a substantial number of patients. If these genes can be linked consistently to recurrence and survival rates, then there will be more certainty that those genes need targeted treatments.