An ICR research team led by Dr Chris Jones uncovered the genetic causes of a rare but lethal form of childhood brain cancer, improving our understanding of the development of the disease. The team discovered a mechanism which drives the development of childhood glioblastoma, opening up the prospect of an effective treatment for the disease for the first time.
About 60 children develop childhood glioblastoma in the UK each year, and no drug treatments are currently available. Glioblastoma is more than one disease, with different types developing at different ages and in different areas of the brain. One type affects younger children aged from about six years and another affects children and young adults aged 13 and over.
The different forms are characterised by different mutations in a histone protein, H3F3A - a gene scaffold protein which controls the activity of other genes. The ICR researchers looked at datasets from patients with the different forms of the disease and showed that the different types of glioblastoma affecting older and younger children had distinct patterns of gene activity.
To investigate the significance of these different histone mutations the team looked at cells taken from a glioblastoma patient with the form of the disease affecting older children, to look at the expression of other genes which may be driven by the mutated form of the histone protein. They discovered that in the cells with this mutation, a potent oncogene (cancer-causing gene) called MYCN was highly active.
Once they found out that this mechanism was involved in the development of this form of glioblastoma, the team ran a large-scale screening experiment to see what might be a good target in blocking the cancer-causing effect of the MYCN gene. They identified a drug target called aurora kinase A, for which drugs are already being developed.
These drugs can now be tested in the particular group of children with glioblastoma who have the histone mutation, and the researchers plan to test these in clinical trials of children within two to three years. Hopefully this opens up the prospect of an effective treatment for the disease for the first time.