Craniopharyngiomas of Adamantinomatous Type Harbor β-Catenin Gene Mutations

Abstract

Craniopharyngioma is a rare tumor occurring in the sellar region comprising 3% of all intracranial tumors. To elucidate the contribution of beta-catenin gene mutation to tumorigenesis, we examined genetic alterations and expression of beta-catenin in 10 cases of adamantinomatous and 6 cases of papillary craniopharyngiomas. Beta-catenin gene mutations were found in all of the adamantinomatous and none of the papillary craniopharyngiomas. Immunohistochemically, all cases of adamantinomatous craniopharyngioma showed cytoplasmic and nuclear expression of beta-catenin. In contrast, papillary craniopharyngiomas showed exclusively membranous expression. The results suggest that adamantinomatous- and papillary-type craniopharyngiomas are not only clinicopathologically, but also genetically, distinctive variants. Mutation of the beta-catenin gene therefore seems to play an important role in the tumorigenesis of adamantinomatous craniopharyngioma. Among the adamantinomatous-type tumors, beta-catenin-positive mesenchymal cells were observed in two cases. Microdissection-based mutational analysis revealed that these mesenchymal cells also harbor the same beta-catenin gene mutations as those of epithelial cells, suggesting their tumorous nature. Thus, at least a subset of adamantinomatous craniopharyngioma is considered to be biphasic.

Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics

“…In addition, cytogenetic abnormalities have been identified in up to 50% of tumors, most commonly gains in 1q, 12q, and 17q [7,8]. Recently, β-catenin gene mutations were found in up to 20% of the rare adamantinomatous craniopharyngiomas, whereas the more common papillary craniopharyngiomas to this date have no common genetic abnormality [9].…”

Cytoplasmic p120ctn Regulates the Invasive Phenotypes of E-Cadherin-Deficient Breast Cancer

“…Immunohistochemistry was performed using 4-m sections of formalin-fixed, paraffin-embedded specimens as described. 29 The sections were autoclaved for antigen retrieval and blocked in either 2% normal swine serum (DAKO Japan, Kyoto, Japan) for lobular carcinoma or M.O.M. mouse IgG blocking reagent (Vector Laboratories, Burlingame, CA) for mouse embryo specimens.…”

60 YEARS OF NEUROENDOCRINOLOGY: Biology of human craniopharyngioma: lessons from mouse models

“…Several studies have used laser capture microdissection (LCM) to separate and analyse specific tumour cell compartments to investigate which ones actually carry the mutation. Sekine et al (2002) reported the presence of the same CTNNB1 mutation in cell clusters and the epithelial tumour tissue that surrounds them in two ACP samples. In contrast, similar LCM analyses by Holsken et al (2009) revealed the presence of different CTNNB1 mutations inside and outside of the clusters in four out of the eight human ACPs analysed, which suggests the existence of tumour heterogeneity and supports a polyclonal origin of the tumours.…”

“…Mouse tumour β-catenin immuno β-catenin immuno 18.5 dpc Mutations in CTNNB1 cause mouse and human ACP Initial molecular studies of human ACP revealed an association with mutations in CTNNB1, the gene that encodes b-catenin, a central regulator of the Wnt pathway (Sekine et al 2002, Kato et al 2004, Buslei et al 2005, Oikonomou et al 2005, Brastianos et al 2014. These mutations were mostly located in exon 3, which encodes amino acids with important regulatory functions (Aberle et al 1997).…”

“…However, two independent groups failed to detect copy number variations in more than 30 ACP and nine PCP tumours; they concluded that chromosomal imbalances are a rare event (Rickert & Paulus 2003, Yoshimoto et al 2004. So far, the most common genetic changes identified in human ACP are mutations in CTNNB1, although mutation frequencies vary from 16 to 100% depending on the study (Sekine et al 2002, Kato et al 2004, Buslei et al 2005, Oikonomou et al 2005, Brastianos et al 2014, Larkin et al 2014. In a recent report, other mutations were identified in several loci by exome sequencing, but they were not recurrent and were possibly not involved in tumour survival or growth (Brastianos et al 2014).…”