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A new target for brain tumour treatments

23 February 2009
Appeared in BioNews 496

A team of scientists in the US have identified genetic changes in specific types of brain tumours. The results, published in the New England Journal of Medicine, may shed light on the mechanism by which the deadly tumours grow.

Each year 200,000 brain tumours are diagnosed in the US, most of which are secondary tumours that have spread from other locations; only 22,000 of them originate in the brain. Most of these are 'gliomas' - tumours that come from the brain's glial cells. Particularly deadly forms of gliomas are glioblastoma multiforme (GBM), which vary in virulence from grade I (benign) to grade IV (rapidly growing and lethal).

The researchers at the Duke University Medical Center, North Carolina, and John Hopkins University, Baltimore, investigated primary GBMs removed from 445 patients and tumours from 494 patients with cancers elsewhere in the body. They analysed the samples for gene changes, in particular IDH1 and 2 - genes coding for isocitrate dehydrogenase enzymes. Changes in the expression of these genes have previously been noted in brain tumours but not in other cancer tissues.

Results indicate that over 70 per cent of the low to mid-range gliomas (grade II - III) had a mutation in the IDH1 gene. These changes decreased the activity of the IDH enzymes. None of the benign gliomas or tumours from the rest of the body had mutations in the IDH genes. The mutations were also rare in the grade IV brain tumours, unless they arose directly from lower grade gliomas. Interestingly, patients with changes in either IDH genes tended to survive an average of 31 months compared to 15 months for glioblastoma patients whose tumours lacked either mutation.

Dr Hai Yan, assistant professor at Duke University's Department of Pathology, was the lead author of the study. He explains that 'all GBMs are basically considered the same and are treated in the same way. Our studies clearly demonstrate that we need to start thinking about them as different'. The implications are that the GBMs could be differentiated between to give specific treatment regimes depending on the type of glioma.

The results also show that the IDH genes may be the 'gate-keeper genes' for certain gliomas, and could be used to identify the cancer-causing defects early. Defining the role of the enzyme in the pathogenesis of glioblastomas could also elucidate a molecular target for brain cancer therapy.

'The results are so clear cut. I have been doing intensive genetic studies in brain cancers for six years, and I have never seen gene mutations as striking as in this study', says Yan.

SOURCES & REFERENCES
Mutations led to deadly brain tumours: study
Reuters |  18 February 2009
Newly discovered gene could be a prime target in most lethal brain cancer
Science Daily |  19 February 2009
Possible genetic flag for brain cancer
Science news |  18 February 2009
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