Genetic analysis of adamantinomatous craniopharyngioma (ACP)

Abstract

From a cohort of 123 ACPs our aim was to gain further information on the molecular genetics and biology of this rare benign tumor entity. DNA was extracted from FFPE-tissue (partly by laser capture microdissection) and CTNNB1 mutational status was analysed by direct sequencing. Even though all ACPs show nuclear ß-catenin accumulation in some tumor cells indicating Wnt pathway activation, only 71% were found mutated at one of the 4 phosphorylation sites in CTNNB1 exon 3. 28 mutated cases were also screened for DDX3X mutations, which can be seen in ˜50% of CTNNB1-mutated medulloblastomas, but none were found. A significantly worse 6-year event-free survival was found in cases mutated at threonine41 compared to cases with other CTNNB1-mutations or cases lacking a mutation. 20 cases were further analysed by molecular inversion profiling, but no larger chromosomal aberrations were found. This method also detected APC-mutations in two cases as a possible alternative mechanism of Wnt activation.