title: Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region.
abstract: Dysregulation of the Wnt signalling pathway contributes to developmental abnormalities and carcinogenesis of solid tumours. Here, we examined beta-catenin and adenomatous polyposis coli (APC) by mutational analysis in pituitary adenomas (n=60) and a large series of craniopharyngiomas (n=41). Furthermore, the expression pattern of beta-catenin was immunohistochemically analysed in a cohort of tumours and cysts of the sellar region including pituitary adenomas (n=58), craniopharyngiomas (n=57), arachnoidal cysts (n=8), Rathke's cleft cysts (n=10) and xanthogranulomas (n=6). Whereas APC mutations were not detectable in any tumour entity, beta-catenin mutations were present in 77% of craniopharyngiomas, exclusively of the adamantinomatous subtype. All mutations affected exon 3, which encodes the degradation targeting box of beta-catenin compatible with an accumulation of nuclear beta-catenin protein. In addition, a novel 81-bp deletion of this exonic region was detected in one case. Immunohistochemical analysis confirmed a shift from membrane-bound to nuclear accumulation of beta-catenin in 94% of the adamantinomatous tumours. Aberrant distribution patterns of beta-catenin were never observed in the other tumour entities under study. We conclude that beta-catenin mutations and/or nuclear accumulation serve as diagnostic hallmarks of the adamantinomatous variant, setting it apart from the papillary variant of craniopharyngioma.
authors.affiliation: Department of Neuropathology, Friedrich-Alexander University Erlangen-Nuremberg, Krankenhausstrasse 8-10, 91054, Erlangen, Germany. rolf.buslei@neuropatho.imed.uni-erlangen.de
authors.forename: Rolf
authors.initials: R
authors.lastname: Buslei
authors.forename: Michael
authors.initials: M
authors.lastname: Nolde
authors.forename: Bernd
authors.initials: B
authors.lastname: Hofmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Meissner
authors.forename: Ilker Y
authors.initials: IY
authors.lastname: Eyupoglu
authors.forename: Florian
authors.initials: F
authors.lastname: Siebzehnrübl
authors.forename: Eric
authors.initials: E
authors.lastname: Hahnen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kreutzer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fahlbusch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003397:Craniopharyngioma / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012658:Sella Turcica / Q000473:pathology*; D015534:Trans-Activators / Q000235:genetics*; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin