Genetic link to child brain tumour

Wednesday September 10 2008

“Childhood cancer genes pinpointed”, reports BBC News website. Scientists have located key genes in the development of the rare brain cancer ependymoma, which is diagnosed in 35 children in the UK every year. It is hoped the discovery could help scientists to find more effective drugs to treat the cancer, which currently has a poor survival rate (only 50%), by targeting the abnormal genes in the cancer cells.

The research found that members of a specific group of genes – the S100 group – were associated with the tumour in the 74 samples tested, with individual genes from the group having associations with particular features, e.g. location of tumour or younger patient age. The research will help in the understanding of this childhood cancer, but much further research is likely to be needed, and any new treatments may still be some way off.

Where did the story come from?

Professor Richard Grundy, Vikki Rand and colleagues of Children’s Brain Tumour Research Centre, University of Nottingham, carried out this research. The study was supported by grants from the Connie and Albert Taylor Trust, The Joseph Foote Foundation and the Birmingham Children’s Hospital Special Trustees. It was published in the peer-reviewed medical journal: British Journal of Cancer .

What kind of scientific study was this?

This laboratory study’s aim was to find genes that might be involved in the childhood brain tumour, ependymoma. The researchers were particularly interested in the genes that lie on the long arm of chromosome 1 (called 1q),  as one of the most common alterations in cancers (including ependymoma) is a “chromosome 1q gain”. This is where the cancer cells gain an extra long chromosome 1 arm.

The researchers used techniques called comparative genome hybridisation (CGH) and serial analysis of gene expression (SAGE) to look at whether they could identify tumours with 1q gains, and to investigate the genes that might be expressed on chromosome 1q in these tumours. They looked at 11 fresh, frozen ependymoma tumour samples (including samples from primary and relapsed tumours from both children and adults), six samples of other types of brain tumour and five healthy tissue samples from various locations in the brain. They compared the gene expression in the tumours that had 1q gain with tumours that did not have 1q gain and with normal brain tissue.

For the genes that were found to be most common in the tumour samples, the researchers used immunochemistry to examine a further 74 paediatric ependymoma tumour samples to look for the protein that that is produced as a result of this gene expression.

What were the results of the study?

The researchers found that of the nine samples examined using CGH, six had a balanced genome (which means no obvious gains or losses of DNA) while three had some extra pieces of DNA (gains). For the two pairs of samples of paediatric relapsed tumours they had, the researchers found that in one of the pairs, there was 1q gain in the relapsed sample but not in the primary sample (the first tumour), while in the other pair of samples, both the primary and the relapsed tumour had balanced genomes. They found that in the relapsed tumour with 1q gain, the genes S100A10 and CH13LI were the most active (unregulated) genes when compared with the relapsed tumour, which had no chromosomal gains. These genes were also more active in this tumour than in normal brain tissue. The researchers also found other members of the S100 family of genes (S100A2, S100A4 and S100A6) were also more active in the tumour with 1q gain.

The researchers went on to look at the proteins produced by these five S100 genes in the 74 other ependymoma samples. In samples where regions of the tumour had undergone cell death (necrosis), there was distinct CH13LI protein staining in the area next to the necrosis. The S100A6 protein was significantly associated with tumours located in the supratentorial region (an area of brain cerebrum located above the cerebellum), while S100A4 was significantly associated with tumours in children under the age of three at the time of diagnosis. Genes S100A6 and S100A10 also demonstrated high levels of expression in the other non-ependymoma brain tumour samples.

What interpretations did the researchers draw from these results?

The researchers conclude that different patterns of activity of the genes S100A4 and S100A6 are associated with clinical subgroups of children with ependymoma, and that protein expression from gene CH13LI is associated with tumour death.

What does the NHS Knowledge Service make of this study?

The research found that activity of members of a specific group of genes – the S100 group – and the CH13LI gene is associated with ependymoma in the 74 samples tested, with single genes of the group having particular associations with various features, e.g. location of tumour or younger patient age. The research is valuable in furthering the understanding of the gene expression in this rare childhood cancer, but further investigation into how the chromosome alterations in question could be linked to the pathological behaviour of this tumour or its adverse prognosis is needed. Although this research provides a useful starting point for these investigations, new treatments may still be some way off.

Sir Muir Gray adds...

This is a dreadful and rare disease. Rare diseases are usually more likely to have genetic causes but the implications for families, based on this research, are still unclear.

Analysis by Bazian
Edited by NHS Choices