Gene fusion is behind deadly brain cancer

Treatment for a lethal form of brain cancer could be on the horizon after the discovery that the cancer can be formed by two genes fusing together. People with the disease could potentially benefit from drugs that block the activity of a protein produced by this wayward fusion.

Cancers can be sparked by a number of genetic mutations, including disruptions to single parts of a gene that either over-stimulate or castrate an important protein. But some cancers arise when two entire genes are accidently fused together during natural cell replication. The protein that the fused genes code for performs some of the functions you would expect of it but does so in new locations or contexts. "They do their thing, but incorrectly," says Anna Lasorella at the Institute for Cancer Genetics at Columbia University, New York.

Lasorella and her colleagues studied the genes involved in a lethal form of brain cancer called glioblastoma. About 3 per cent of the glioblastoma tumours they looked at were caused by the fusing of two genes.

On its own, each gene has an important but benign function. When fused together the two wreak havoc during cell division. The protein that the fused genes code for latches onto the spindles that pull freshly replicated chromosomes into two new cells during cell division. The interference means that instead of an even division, the cells end up with different numbers of chromosomes: a phenomenon known as aneuploidy. "It's a well-known hallmark of cancer," says Antonio Iavarone, also at Columbia.

Having identified this mechanism, the team wanted to check that the fused genes actually cause this form of cancer. So they injected the newly formed protein into the brains of healthy mice. Ninety per cent of the mice went on to develop the expected glioblastomas.

The team then administered a drug that blocked the activity of the new protein. In doing so, they were able to double the mice's survival time.

Because the protein is specific to the cancer cells, the team predicts that drugs to target it would cause minimal damage to healthy cells.

Journal reference: Science, DOI: 10.1126/science.1220834

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