Endocrine Abstracts

Craniopharyngiomas (CPs) are tumours located in the sellar and parasellar region, thought to have an embryonic origin and/or to arise from pituitary progenitors/stem cells. They have an overall incidence of 1–2 new cases/million population/per year and are subdivided into two histologically different subtypes, adamantinomatous (aCPs) and papillary (pCPs). The clinical manifestations at diagnosis for CPs are: headache, visual disturbances, polyuria/polydipsia, endocrine dysfunction such as growth retardation, puberty disturbances and obesity. The current therapy of choice is complete resection or partial resection with the intention to maintain optic nerve and hypothalamic functions if these areas are affected. Overall surgical survival rates are high (90%), although post-surgical morbidity is present in 100% of the patients, leading endocrine deficiencies and lifelong treatment. Recently, molecular studies have identified that the two CPs subtypes are genetically distinct with aCPs mainly harboring mutations in Wnt signaling effector, β-catenin, and pCPs in the BRAFV600E oncogene. These molecular findings have led to the identification of possible therapeutic treatments for pCPs using BRAF inhibitors, which highlights the importance genetic studies for the identification of future targeted therapies. Transgenic murine models of aCPs have revealed novel therapeutic targets that could be beneficial for aCP treatments and identified pathways important in tumour progression both in humans and murine models. Moreover, we present genetic studies from a large cohort of aCP patients that suggests that the reported mutual genetic exclusivity of CPs subtypes, is in fact more heterogeneously complex than previously thought, and that the underlying genetic drivers for a large proportion of CPs patients remains unknown.