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Very low tumor mutation burden identifies inflamed recurrent glioblastomas responsive to cancer immunotherapy

ABSTRACT: Very low tumor mutation burden identifies inflamed recurrent glioblastomas responsive to cancer immunotherapy

PROVIDER: PRJNA668404 | ENA |

REPOSITORIES: ENA

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Very low tumor mutation burden identifies inflamed recurrent glioblastomas responsive to cancer immunotherapy

Project description:Very low tumor mutation burden identifies inflamed recurrent glioblastomas responsive to cancer immunotherapy

| PRJNA668405 | ENA

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.

Project description:Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients. A relationship between tumor mutation burden and survival is not observed in cohorts of immunotherapy naïve newly diagnosed or recurrent glioblastoma patients. Transcriptomic analyses reveal an inverse relationship between tumor mutation burden and enrichment of inflammatory gene signatures in cohorts of recurrent, but not newly diagnosed glioblastoma tumors, implying that a relationship between tumor mutation burden and tumor-intrinsic inflammation evolves upon recurrence.

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DNA methylation patterns in IDH-wildtype de novo Glioblastomas at first occurrence (primary) and relapsed (recurrent) disease

Project description:Genome-wide DNA methylation pattern was interrogated in glioblastomas at first diagnosis and at disease relapse, utilizing the Illumina 450K Methylation Bead Array

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RNA-seq of biopsies, crypts and organoids of inflamed and non-inflamed biopsies of ulcerative colitis patients

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Parametric response maps of perfusion MRI may identify recurrent glioblastomas responsive to bevacizumab and irinotecan.

Project description:BackgroundPerfusion weighted imaging (PWI) can be used to measure key aspects of tumor vascularity in vivo and recent studies suggest that perfusion imaging may be useful in the early assessment of response to angiogenesis inhibitors. Aim of this work is to compare Parametric Response Maps (PRMs) with the Region Of Interest (ROI) approach in the analysis of tumor changes induced by bevacizumab and irinotecan in recurrent glioblastomas (rGBM), and to evaluate if changes in tumor blood volume measured by perfusion MRI may predict clinical outcome.Methods42 rGBM patients with KPS ≥ 50 were treated until progression, as defined by MRI with RANO criteria. Relative cerebral blood volume (rCBV) variation after 8 weeks of treatment was calculated through semi-automatic ROI placement in the same anatomic region as in baseline. Alternatively, rCBV variations with respect to baseline were calculated into the evolving tumor region using a voxel-by-voxel difference. PRMs were created showing where rCBV significantly increased, decreased or remained unchanged.ResultsAn increased blood volume in PRM (PRMCBV+) higher than 18% (first quartile) after 8 weeks of treatment was associated with increased progression free survival (PFS; 24 versus 13 weeks, p = 0.045) and overall survival (OS; 38 versus 25 weeks, p = 0.016). After 8 weeks of treatment ROI analysis showed that mean rCBV remained elevated in non responsive patients (4.8 ± 0.9 versus 5.1 ± 1.2, p = 0.38), whereas decreased in responsive patients (4.2 ± 1.3 versus 3.8 ± 1.6 p = 0.04), and re-increased progressively when patients approached tumor progression.ConclusionsOur data suggest that PRMs can provide an early marker of response to antiangiogenic treatment and warrant further confirmation in a larger cohort of GBM patients.

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Genotyping by array of 123 IDH WT glioblastomas

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Mutations in IDH1 are associated with DNA hypermethylation in glioblastomas

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