Comprehensive molecular characterization of craniopharyngiomas using whole transcriptome and spatial transcriptomics approaches

Kert, Špela (author), Matjašič, Alenka (author), Pižem, Jože (author), Mlakar, Jernej (author), Bošnjak, Matic (author), Jerala, Miha (author), Kotnik, Primož (author), Faganel Kotnik, Barbara (author), Kitanovski, Lidija (author), Zupan, Andrej (author)

Craniopharyngiomas (CPs) are rare benign brain tumors that are classified as WHO grade I, with two subtypes: adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP). ACP is caused by somatic mutations in exon 3 of the CTNNB1 gene activating the Wnt signaling pathway. PCP is associated with somatic BRAF p.V600E mutations activating the MAPK signaling pathway. Understanding their molecular differences is crucial for diagnosis and treatment. This study aimed to analyze common somatic alterations in ACP and PCP using bulk transcriptome sequencing and in situ spatial transcriptomics. RNA sequencing and high-resolution spatial profiling were used to detect mutations and examine gene expression differences among ACP, PCP, and healthy pituitary tissue. Whole transcriptome sequencing was performed on 24 tumor samples, with healthy pituitary data from the GTEx portal. Bioinformatics analysis utilized the CTAT mutation pipeline, with Sanger sequencing for validation. Results confirmed BRAF p.V600E mutations in all PCP samples and CTNNB1 mutations in all ACP samples. Differential gene expression analysis highlighted distinct molecular profiles and reinforced the involvement of Wnt and MAPK signaling. Spatial profiling identified 41 differentially expressed genes between ACP and PCP. This study provides critical insights into CP biology, supporting improved diagnostics and potential therapeutic strategies.

• Language: English
• Keywords: craniopharyngioma, differential gene expression, in situ spatial profiling, somatic mutation detection, transcriptional analysis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: Str. 130–142
• Numbering: Vol. 42, iss. 4
• PID: 20.500.12556/RUL-178846
• UDC: 61
• ISSN on article: 1433-7398
• DOI: 10.1007/s10014-025-00509-z
• COBISS.SI-ID: 243867907
• Publication date in RUL: 30.01.2026

Record is a part of a journal

• Title: Brain tumor pathology
• Shortened title: Brain tumor pathol.
• Publisher: Springer Nature, The Japan Society of Brain Tumor Pathology
• ISSN: 1433-7398
• COBISS.SI-ID: 514824217

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: kraniofaringiom, diferencialna genska ekspresija, prostorsko profiliranje in situ, odkrivanje somatskih mutacij, transkripcijska analiza

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0054
• Name: Patologija in molekularna genetika