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

Area of Science:

• Neuro-oncology
• Molecular Biology
• Genomics

Background:

• Craniopharyngiomas (CPs) are rare WHO grade I brain tumors with two subtypes: adamantinomatous (ACP) and papillary (PCP).
• ACP is linked to CTNNB1 mutations activating Wnt signaling.
• PCP is associated with BRAF p.V600E mutations activating MAPK signaling.

Purpose of the Study:

• To analyze common somatic alterations in ACP and PCP.
• To compare molecular profiles of ACP, PCP, and healthy pituitary tissue.
• To identify distinct gene expression patterns between CP subtypes.

Main Methods:

• Whole transcriptome sequencing of 24 tumor samples and GTEx pituitary data.
• Bioinformatics analysis using the CTAT mutation pipeline and Sanger sequencing validation.
• In situ spatial transcriptomics for high-resolution gene expression profiling.

Main Results:

• Confirmed BRAF p.V600E mutations in all PCP samples and CTNNB1 mutations in all ACP samples.
• Differential gene expression analysis revealed distinct molecular profiles, reinforcing Wnt and MAPK pathway involvement.
• Spatial profiling identified 41 differentially expressed genes between ACP and PCP.

Conclusions:

• The study elucidates key molecular distinctions between ACP and PCP subtypes.
• Findings support improved diagnostic approaches for craniopharyngiomas.
• Identified molecular differences offer potential targets for novel therapeutic strategies.