Genetics Of Children's Brain Tumour Unlocked

Genetics Of Children's Brain Tumour Unlocked
Main Category: Cancer / Oncology
Also Included In: Pediatrics / Children's Health; Neurology / Neuroscience; Genetics
Article Date: 18 May 2010 - 5:00 PDT


Researchers have identified an important cancer gene that could lead to more effective drugs being developed to fight paediatric high grade glioma, a disease which currently has a poor prognosis. The discovery, published today in the Journal of Clinical Oncology, was one of a number of significant genetic differences found between the adult and youth form of the disease.

Clinicians and scientists at The Institute of Cancer Research (ICR) and the University of Nottingham, on behalf of the UK Children's Cancer and Leukaemia Group, and St Jude Children's Research Hospital in the US conducted by far the most comprehensive analysis to date of paediatric high-grade glioma, making a detailed scan of the genome of 78 newly-diagnosed patients.

They compared these paediatric tumour samples with the genome of adult gliomas, looking through 500,000 individual pieces of DNA for variations in the number of copies of each. In paediatric gliomas, a gene called PDGFRA on chromosome 4q12 was commonly amplified and there were often extra copies of chromosome 1q. These changes are rarely seen in the adult form of the disease.

Clinical differences between gliomas in adults and youth had already been observed, for example growth in disparate areas of the brain, but this is the first study to establish that the underlying genetics differ.

"We found significant differences between the genomes of adult and young people's gliomas," says Dr Chris Jones, Leader of the Paediatric Molecular Pathology Team at the ICR. "This is an important finding because it means studies on adult gliomas cannot simply be applied to younger patients, and it has particular implications for drug trials."

The researchers also tracked gene activity in 53 of the tumour samples, and compared the results with adult gliomas. Paediatric glioma tumours that did not have the PDGFRA alteration were nevertheless found to have associated genes switched on, suggesting that this biological pathway is a key to the development of this childhood cancer. The PDGFRA gene carries instructions for making a protein found on the cell surface, which is part of a pathway that helps control cell growth, proliferation and survival - processes that are commonly disrupted in cancer.

"This cancer gene is unusually active in paediatric high-grade gliomas and is likely to be an important drug target," says Professor Richard Grundy from the Children's Brain Tumour Research Centre at the University of Nottingham.

In addition, ten children in the study had glioma that arose after they were treated with radiotherapy to the brain for a previous cancer. Analysis of these children's tumours revealed they had the gene alterations at even higher frequency than the other cancers studied, which had been triggered by other factors. The presence of these alterations irrespective of the trigger for the cancer also indicates that they are crucial to glioma development.

The work was funded by the Children's Brain Tumor Foundation, the National Institutes of Health, the National Brain Tumor Society, the Ryan McGee Foundation, Musicians Against Childhood Cancer, the Noyes Brain Tumor Foundation, ALSAC, Samantha Dickson Brain Tumour Trust, Air and Ground, The Connie and Albert Taylor Trust, the Joe Foote Foundation, Cancer Research UK and the NHS.

Notes

- High grade gliomas account for about 75 to 80 per cent of primary malignant brain tumours (cancer that originates in the brain)

- In the UK, about 4,550 adults and 350 children are diagnosed with brain tumours each year. Gliomas are the most common brain tumour in children

- Aggressive gliomas can be very difficult to treat successfully and sadly 70 to 90 per cent of patients die within two years of diagnosis

The Children's Brain Tumour Research Centre (CBTRC)

- The Children's Brain Tumour Research Centre (CBTRC) at the University of Nottingham brings together researchers from clinical and basic science arenas, both locally and Internationally.

- The activity of the centre is directed at increasing our understanding of the biological nature of childhood and adolescent brain tumours and using this knowledge to optimize the health outcomes for the child and family

- Researchers in the CBTRC are currently testing hypotheses concerned with neurodevelopment, the application of novel imaging and genetic techniques aimed at comprehensive assessment of tumour biology, optimisation of drug selection and CNS targeting.

- Major funders of the Joe Foote Foundation and the Samantha Dickson Brain Tumour Trust.

Source
Institute of Cancer Research (ICR)

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Genetics Of Children's Brain Tumour Unlocked