Genetic drivers of rare brain tumours

Craniopharyngiomas are rare, benign brain tumours with potentially devastating clinical effects, including visual defects, severe headaches, impaired intellectual function and obesity. Because of their location in the brain it can be difficult to remove the tumours surgically, which makes their treatment complicated.

A team of researchers from the United States, led by Priscilla Brastianos from the Massachusetts General Hospital and Sandro Santagata from Brigham and Women's Hospital, Boston, Massachusetts, and including Hala Taha from the Children's Cancer Hospital Egypt, sequenced the protein-coding genes of DNA from craniopharyngioma tumours from 15 patients. This was followed by targeted sequencing of DNA from 98 tumours from 95 additional patients.

There are two subtypes of craniopharyngioma: the adamantinomatous form, which is most common in children, and the papillary form, which occurs predominantly in adults. The results of the sequencing, which are published in Nature Genetics, showed that 96% of adamantinomatous tumours contained mutations in one gene — CTNNB1 — whereas 95% of papillary tumours contained a recurrent mutation in another gene, BRAF.

Neither subtype showed recurrent mutations in any other genes, which suggests that mutations in the two genes identified are instrumental in the growth of these tumours. The BRAF mutation is the first reported genetic alteration associated with the papillary subtype.

The BRAF mutation reported has also been found in melanomas and other brain tumours, and BRAF inhibitors have shown great promise in treating some of these tumours. As well as helping clinicians to identify which type of craniopharyngioma a patient has, these findings might also lead to new therapeutic strategies.

"We are hoping to take these results to clinical trials," says Brastianos, who plans to continue working with Santagata to evaluate BRAF inhibitors in patients with papillary craniopharyngiomas.

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