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Dissecting the tumour microenvironment displays different genomic profile in patients treated with carmustine wafers.

ABSTRACT: Dissecting the tumour microenvironment displays different genomic profile in patients treated with carmustine wafers.

PROVIDER: PRJNA819959 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18477890.fastq.gz	Fastqsanger.gz
	SRR18477891.fastq.gz	Fastqsanger.gz
	SRR18477892.fastq.gz	Fastqsanger.gz
	SRR18477893.fastq.gz	Fastqsanger.gz
	SRR18477894.fastq.gz	Fastqsanger.gz

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Dissecting the tumour microenvironment displays different genomic profile in patients treated with carmustine wafers.

Project description:Despite the state-of-the art treatment, consisting of surgery followed by chemo and radiotherapy, patients diagnosed for a glioblastoma multiforme (GBM), have a median overall survival of 14 months. The lack of therapeutic efficacy is due to the great inter- and intra-tumour cellular and molecular heterogeneity, the biological aggressiveness, the ability to develop drug resistance as well as the infiltrative nature of tumour cells into the surrounding brain parenchyma. Furthermore, it has been widely shown that GBM progression is supported not only by tumour cells, but also by their interaction with the surrounding microenvironment. In the late 90s, a novel adjuvant therapy has been approved involving the placement, in the resection cavity, of wafers delivering carmustine (CW). Although reported studies are contrasting a retrospective study, performed in our Institute, revealed that the treatment of 116 GBM patients by CW showed 17% of long-term survivors (OS >36 months). We isolated glioma-associated stem cells (GASC), resident in the glioma microenvironment, from tumour samples of 3 patients responsive and 3 patients not responsive to CW implantation and we performed a transcriptomic analysis to identify differentially expressed genes. We found that GASC derived from the two classes of patients have distinctive transcriptomic profiles and we selected 78 differentially expressed genes to explore and validate their expression in more GASC cell lines. We identified four genes specifically downregulated in GASC isolated from patients with longer OS (>30 months). These genes showed a correlation with clinical data deposited in TCGA-GBM dataset.

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