Craniopharyngiomas are epithelial tumors that arise in the pituitary stalk along the path of the craniopharyngeal duct. There are two main subtypes of craniopharyngiomas, the adamantinomatous form that is more common in children and the papillary form that predominantly occurs in adults. Craniopharyngiomas can cause profound clinical sequelae both through mass effect at presentation and through morbidity of treatment. Attempted surgical resection is usually the initial treatment of craniopharyngioma, but because these tumors adhere to critical brain and vascular structures, incomplete resection is common. Incompletely excised tumors have a propensity to recur, frequently with cysts, with firm adhesions between the recurrent tumor and the surrounding structures such that curative surgery is exceedingly difficult. As a result, most patients suffer lifelong sequelae. Radiation therapy, often used as an adjunct after surgery, can contribute to these complications. No effective treatment besides surgery and radiation is known for craniopharyngiomas, and incomplete knowledge of the molecular mechanisms that drive craniopharyngiomas has hampered the development of targeted therapies for this tumor.
In collaboration with Sandro Santagata, we comprehensively characterize craniopharyngiomas (Brastianos et al. Nature Genetics 2014). We identified mutations in CTNNB1 in nearly all adamantinomatous craniopharyngiomas examined (62/65, 95%) and recurrent mutations in BRAF (resulting in p.Val600Glu) in nearly all papillary craniopharyngiomas (39/42, 93%). The CTNNB1 and BRAF mutations were clonal in each tumor subtype, and we detected no other recurrent mutations or genomic aberrations in either subtype. These findings have important implications for the diagnosis and treatment of these neoplasms.