Integrated Transcriptomic and CRISPR Dependency Analysis Prioritizes a CDK1-AURKB Mitotic Vulnerability Axis in Diffuse Intrinsic Pontine Glioma

Diffuse intrinsic pontine glioma (DIPG), a lethal pediatric brainstem tumor, remains without many treatment options. Researchers combined public DIPG transcriptomic datasets, protein-protein interaction modeling, functional enrichment, immune deconvolution, survival analysis, and CRISPR dependency data from the DepMap database to identify potential mitotic vulnerabilities.

By comparing DIPG tumors with brainstem low-grade glioma samples, they discovered a transcriptional program related to chromosome segregation, nuclear division, and the cell cycle. A network analysis highlighted a mitotic hub module comprising CDK1, AURKB, TOP2A, CDC20, CDCA8, and other G2/M regulators. Although immune-cell fractions showed low cytotoxic T-cell signals, indicating an immune-cold phenotype, further orthogonal validation is needed.

Survival analysis did not find any significant relationship between inferred immune scores or a composite mitotic hub score and overall survival. The CRISPR gene-effect data from the DepMap database identified CDK1, AURKB, TOP2A, and BIRC5 as potential dependencies in various brain tumor models. This computational approach offers a framework for prioritizing mitotic vulnerabilities in DIPG, paving the way for experimental validation in relevant disease models.