The aim of this study was to investigate the noninvasive MRI-based radiomics diagnosis to detect BRAF and CTNNB1 mutations in craniopharyngioma patients.
Papillary craniopharyngiomas are defined by BRAF <sup>V600E</sup> mutations while β-catenin alterations characterize adamantinomatous craniopharyngiomas.
Sixteen craniopharyngiomas were further analyzed by molecular inversion profiling (MIP); 76.1% of the ACP were mutated in exon 3 of CTNNB1 encoding for β-catenin and there was a trend towards a worse event-free survival in cases mutated at Thr41.
We aimed to study BRAF and CTNNB1 gene mutations in CPs operated at our institute, and correlate it with clinicopathological parameters including histopathology and immunohistochemistry (IHC) for proteins VE-1 and β-catenin.
In order to achieve further insights distinguishing CP variants, we conducted whole genome methylation (450 k array) and microarray-based gene expression studies in addition to CTNNB1 and BRAF mutation analysis using a comprehensive cohort of 80 adaCP and 35 papCP.
Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors).
Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors).
Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors).
Our findings provide insights into the role of the Wnt pathway in normal pituitary development and demonstrate a causative role for mutated β-catenin in an undifferentiated RP progenitor in the genesis of murine and human craniopharyngioma.
The objective of this study is to perform the molecular analysis of HESX1, PROP1, POU1F1, and CTNNB1 genes and evaluate a panel of miRNA expression in craniopharyngioma.
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.
Since this gene product is involved with development, these results suggest that beta-catenin mutations may contribute to the initiation and subsequent growth of congenital craniopharyngiomas.
The other unusual adamantinomatous type and squamous papillary type craniopharyngiomas showed no obvious nuclear/cytoplasmic beta-catenin immunoreactivity and no mutation of the beta-catenin gene, suggesting molecular heterogeneity.
Although established approaches along with new surgical and radiotherapeutic approaches remain the main treatment modalities, recent evidence has provided insight into their molecular pathogenesis involving, other than chemotherapy, treatments with targeted agents as in gliomas and craniopharyngiomas bearing BRAF mutations.
In conclusion, mutation profiles of BRAF wild-type craniopharyngiomas and ameloblastomas share mutations of FGFR genes and have additional mutations with potential for targeted therapy.
A thorough analysis of the alterations of β-catenin/CTNNB1 and BRAF genes investigated in 1123 CP cases included in 27 studies, showed that, on average, CTNNB1 mutations were present in two-thirds of adamantinomatous CPs and BRAF mutations in 90% of papillary CPs.