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

TL;DR

This study uses advanced sequencing techniques to uncover molecular differences between two types of craniopharyngiomas, aiding in better diagnosis and treatment.

Contribution

The study provides a comprehensive molecular characterization of craniopharyngioma subtypes using whole transcriptome and spatial transcriptomics.

Findings

All PCP samples had BRAF p.V600E mutations, while all ACP samples had CTNNB1 mutations.

Differential gene expression analysis revealed distinct molecular profiles linked to Wnt and MAPK pathways.

Spatial profiling identified 41 differentially expressed genes between ACP and PCP.

Abstract

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.

The online version contains supplementary material available at 10.1007/s10014-025-00509-z.

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