Link between gene variant and brain tumour growth revealed

The link between a certain genetic mutation and the most common form of brain tumour has been unravelled by US scientists. The mutation, in a gene called IDH1, was already known to be associated with the development of brain cancers, but it was not known how the mutation contributed to the disease.

Gliomas are the most common type of brain tumour, accounting for around 80 per cent of the 4,500 brain cancers that are diagnosed in the UK each year. Approximately 70 per cent of people diagnosed with gliomas have a specific mutation in their IDH1 gene, but until now scientists did not understand how this mutation contributed to glioma formation. In the new study, a team of researchers from Agios Pharmaceuticals, Cambridge, Massachusetts, US, found that glioma patients carrying the IDH1 mutation had abnormally high production of a chemical called 2-hydroxyglutarate (2HG) in their brain.

In a report published in the journal Nature, the scientists compared levels of 2HG in tumour cells from glioma patients who carried the IDH1 mutation to 2HG levels in tumour cells from glioma patients who did not have the IDH1 mutation. Those that carried the IDH1 mutation had more than 100 times more 2HG in their glioma tumour cells than those that did not. This new evidence reveals that the mutated IDH1 gene can act as an oncogene, that is, a gene that contributes to directly to the development of cancer.

Professor Lew Cantley, a founder of Agios Pharmaceuticals, said: 'The team at Agios has demonstrated that what was previously considered an inactive [gene] is in reality an active oncogene and a potential therapeutic target. This has fundamentally changed our understanding of the field'. He added that the 'easily measured' marker, 2HG, will help in 'the diagnosis and treatment' of gliomas and other IDH1-related tumours. By finding a way to block 2HG production in the tumour cells, scientists may be able to develop a new treatment for gliomas.

Dr Laura Bell, science information officer at Cancer Research UK, said: 'This study has brought exciting new information to light which could eventually help doctors understand more about how certain brain tumours are likely to progress - and how best to treat them'. However, she cautioned: 'There is still some way to go before this new information could be used to help treat people with cancer'.