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Drug-class specific gene-based MAPK sensitivity scores predict sensitivity to MAPK inhibitors in pediatric low-grade gliomas

ABSTRACT: Drug-class specific gene-based MAPK sensitivity scores predict sensitivity to MAPK inhibitors in pediatric low-grade gliomas

PROVIDER: PRJNA923658 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23074130.fastq.gz	Fastqsanger.gz
	SRR23074131.fastq.gz	Fastqsanger.gz
	SRR23074132.fastq.gz	Fastqsanger.gz
	SRR23074133.fastq.gz	Fastqsanger.gz
	SRR23074134.fastq.gz	Fastqsanger.gz

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Drug-class specific gene-based MAPK sensitivity scores predict sensitivity to MAPK inhibitors in pediatric low-grade gliomas

Project description:Pediatric low-grade gliomas (pLGG) have shown heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. A predictive feature for stratification is needed to identify patients likely to benefit from MAPKi therapy. MAPK-related genes differentially regulated between MAPKi sensitive and non-sensitive cell lines from the Genomics of Drug Sensitivity in Cancer dataset identified class-specific MAPKi sensitivity gene signatures used to calculate the MAPKi sensitivity score (MSS) via single sample gene set enrichment analysis. The MSS discerned gliomas with varying MAPK alterations from those without, and was higher in pLGG compared to other pediatric CNS tumors. As in clinical trials, the MSS was heterogeneous within pLGGs with a common MAPK alteration. A positive correlation between the MSS and the predicted immune infiltration determined by the ESTIMATE signature was observed. The MSS therefore represents a potential tool for the stratification of pLGG patients, worth of further investigation in upcoming clinical trials. Our data could support a role of microglia in the response to MAPKi, warranting further validation.

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Project description:MAPK inhibitor sensitivity scores (MSS) were developed to predict sensitivity to MAPK inhibitors in pediatric low-grade gliomas (pLGG). The scores were validated in pLGG cell lines in vitro and in the publicly available Open Pediatric Brain Tumor Atlas dataset. Validation in independent datasets is warranted.

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