This SuperSeries is composed of the SubSeries listed below.
Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951.
Sex, Age, Specimen part
View SamplesBackground: Intrinsic glioma subtypes (IGS) are molecularly similar tumors that can be identified based on unsupervised gene-expression analysis. Here, we have evaluated the clinical relevance of these subtypes within EORTC26951, a randomized phase III clinical trial investigating adjuvant procarbazine, CCNU (lomustine) and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study is the first to include gene-expression profiles of formalin-fixed and paraffin-embedded (FFPE) clinical trial samples. Methods: Gene-expression profiling was performed in 140 samples: 47 fresh frozen and 93 FFPE, on HU133_Plus_2.0 and HuEx_1.0_st arrays (Affymetrix), respectively. Results: All previously identified six intrinsic glioma subtypes are present in EORTC26951. This confirms that different molecular subtypes are present within a well-defined histological subtype. Intrinsic subtypes are highly prognostic for overall- (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance, tumor location), molecular (1p19qLOH, IDH1 mutation, MGMT methylation) and histological parameters. Combining known molecular (1p19LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (Proportion of Explained Variation 30% v 23%). Specific genetic changes (IDH1, 1p19qLOH and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p19qLOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone v 12.8 years after RT/PCV; P=0.0349; HR 2.18, 95% CI [1.06, 4.50]. Conclusion: Intrinsic subtypes are highly prognostic in EORTC26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV
Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951.
Sex, Age, Specimen part
View SamplesBackground: Intrinsic glioma subtypes (IGS) are molecularly similar tumors that can be identified based on unsupervised gene-expression analysis. Here, we have evaluated the clinical relevance of these subtypes within EORTC26951, a randomized phase III clinical trial investigating adjuvant procarbazine, CCNU (lomustine) and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study is the first to include gene-expression profiles of formalin-fixed and paraffin-embedded (FFPE) clinical trial samples. Methods: Gene-expression profiling was performed in 140 samples: 47 fresh frozen and 93 FFPE, on HU133_Plus_2.0 and HuEx_1.0_st arrays (Affymetrix), respectively. Results: All previously identified six intrinsic glioma subtypes are present in EORTC26951. This confirms that different molecular subtypes are present within a well-defined histological subtype. Intrinsic subtypes are highly prognostic for overall- (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance, tumor location), molecular (1p19qLOH, IDH1 mutation, MGMT methylation) and histological parameters. Combining known molecular (1p19LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (Proportion of Explained Variation 30% v 23%). Specific genetic changes (IDH1, 1p19qLOH and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p19qLOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone v 12.8 years after RT/PCV; P=0.0349; HR 2.18, 95% CI [1.06, 4.50]. Conclusion: Intrinsic subtypes are highly prognostic in EORTC26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV
Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951.
Sex, Age, Specimen part
View SamplesBackground: Intrinsic glioma subtypes (IGS) are molecularly similar tumors that can be identified based on unsupervised gene-expression analysis. Here, we have evaluated the clinical relevance of these subtypes within EORTC26951, a randomized phase III clinical trial investigating adjuvant procarbazine, CCNU (lomustine) and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study is the first to include gene-expression profiles of formalin-fixed and paraffin-embedded (FFPE) clinical trial samples. Methods: Gene-expression profiling was performed in 140 samples: 47 fresh frozen and 93 FFPE, on HU133_Plus_2.0 and HuEx_1.0_st arrays (Affymetrix), respectively. Results: All previously identified six intrinsic glioma subtypes are present in EORTC26951. This confirms that different molecular subtypes are present within a well-defined histological subtype. Intrinsic subtypes are highly prognostic for overall- (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance, tumor location), molecular (1p19qLOH, IDH1 mutation, MGMT methylation) and histological parameters. Combining known molecular (1p19LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (Proportion of Explained Variation 30% v 23%). Specific genetic changes (IDH1, 1p19qLOH and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p19qLOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone v 12.8 years after RT/PCV; P=0.0349; HR 2.18, 95% CI [1.06, 4.50]. Conclusion: Intrinsic subtypes are highly prognostic in EORTC26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV
Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951.
Sex, Age, Specimen part
View SamplesBackground: Intrinsic glioma subtypes (IGS) are molecularly similar tumors that can be identified based on unsupervised gene-expression analysis. Here, we have evaluated the clinical relevance of these subtypes within EORTC26951, a randomized phase III clinical trial investigating adjuvant procarbazine, CCNU (lomustine) and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study is the first to include gene-expression profiles of formalin-fixed and paraffin-embedded (FFPE) clinical trial samples. Methods: Gene-expression profiling was performed in 140 samples: 47 fresh frozen and 93 FFPE, on HU133_Plus_2.0 and HuEx_1.0_st arrays (Affymetrix), respectively. Results: All previously identified six intrinsic glioma subtypes are present in EORTC26951. This confirms that different molecular subtypes are present within a well-defined histological subtype. Intrinsic subtypes are highly prognostic for overall- (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance, tumor location), molecular (1p19qLOH, IDH1 mutation, MGMT methylation) and histological parameters. Combining known molecular (1p19LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (Proportion of Explained Variation 30% v 23%). Specific genetic changes (IDH1, 1p19qLOH and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p19qLOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone v 12.8 years after RT/PCV; P=0.0349; HR 2.18, 95% CI [1.06, 4.50]. Conclusion: Intrinsic subtypes are highly prognostic in EORTC26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV
Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951.
Sex, Age, Specimen part
View SamplesBackground: Intrinsic glioma subtypes (IGS) are molecularly similar tumors that can be identified based on unsupervised gene-expression analysis. Here, we have evaluated the clinical relevance of these subtypes within EORTC26951, a randomized phase III clinical trial investigating adjuvant procarbazine, CCNU (lomustine) and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study is the first to include gene-expression profiles of formalin-fixed and paraffin-embedded (FFPE) clinical trial samples. Methods: Gene-expression profiling was performed in 140 samples: 47 fresh frozen and 93 FFPE, on HU133_Plus_2.0 and HuEx_1.0_st arrays (Affymetrix), respectively. Results: All previously identified six intrinsic glioma subtypes are present in EORTC26951. This confirms that different molecular subtypes are present within a well-defined histological subtype. Intrinsic subtypes are highly prognostic for overall- (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance, tumor location), molecular (1p19qLOH, IDH1 mutation, MGMT methylation) and histological parameters. Combining known molecular (1p19LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (Proportion of Explained Variation 30% v 23%). Specific genetic changes (IDH1, 1p19qLOH and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p19qLOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone v 12.8 years after RT/PCV; P=0.0349; HR 2.18, 95% CI [1.06, 4.50]. Conclusion: Intrinsic subtypes are highly prognostic in EORTC26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV
Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951.
Sex, Age, Specimen part
View SamplesData on the temporal dynamics of human placental gene expression is scarce. We have completed the first whole-genome profiling of human placental gene expression dynamics (GeneChips, Affymetrix) from early to mid- gestation (10 samples; gestational weeks 5 to 18) and report 154 genes with considerable change in transcript levels (FDR P<0.1). Functional enrichment analysis revealed >200 GO categories that are statistically over-represented among 105 genes with dynamically increasing transcript levels. Analysis in an extended sample (n=43; gestational weeks 5 to 41) conformed a highly significant (FDR P<0.05) expressional peak in mid-gestation placenta for ten genes: BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10, STC1. A central hypothesis of our study states that the aberrant expression of genes characteristic to mid-gestation placenta may contribute to affected fetal growth, maternal preeclampsia (PE) or gestational diabetes (GD). The gene STC1 coding for Stanniocalcin 1 (STC1) was identified with a sharp placental expressional peak in mid-gestation, increased mRNA levels at term and significantly elevated STC1 protein levels in post-partum maternal plasma in all pregnancy complications. The highest STC1 levels were identified in women, who developed simultaneously PE and delivered an SGA baby (median 731 vs 418 pg/ml in controls; P=0.001). CCNG2 and LYPD6 exhibited significantly increased placental mRNA expression and enhanced intensity of immunohistochemistry staining in placental sections all studied in GD and PE cases. Aberrant expression of mid-gestation specific genes in pregnancy complications at term indicates the importance of the fine-scale tuning of the temporal dynamics of transcription regulation in placenta. Observed significantly elevated plasma STC1 in complicated pregnancies warrants further investigations of its potential as a biomarker. Interestingly, a majority of genes with high expression in mid-gestation placenta have also been implicated in adult complex disease. This observation promotes a recently opened discussion on the role of placenta in developmental programming.
Mid-gestational gene expression profile in placenta and link to pregnancy complications.
Specimen part
View SamplesCbtOE (Tim-gal4; UAS-cbtFLAG), Tim-gal4 (control for CbtOE), cbtRNAi (Tim-gal4-UAS-Dcr2-UAS-cbtIR-cbtE1) and Tim-gal4;UAS-Dcr2 (control for CbtRNAi) flies. Flies were entrained in LD (light: dark) condition for 3-4 days and harvested at six time points: ZT3, ZT7, ZT11, ZT15, ZT19, ZT23 Fly heads were collected, RNA was extracted and RNA-seq libraries were prepared as previously described (Engreitz et al., 2013) Overall design: Three samples of cbtRNAi and three samples of their controls. Two samples of cbtOE with two samples of their controls.
The transcription factor Cabut coordinates energy metabolism and the circadian clock in response to sugar sensing.
Specimen part, Subject, Time
View SamplesMaintaining metabolic homeostasis in response to fluctuating nutrient intake requires intricate coordination between tissues of multicellular animals. The insulin/glucagon axis is well known to hormonally coordinate organism-wide carbohydrate metabolism. The ChREBP/Mondo-Mlx transcription factors regulate glycolytic and lipogenic genes locally in hepatocytes and adipocytes, but its role in systemic metabolic homeostasis has remained poorly understood. We demonstrate that Mondo-Mlx controls gene activity in several peripheral tissues of Drosophila melanogaster, where it regulates nutrient digestion and transport as well as carbohydrate, amino acid and lipid metabolism. In addition to directly regulating metabolic genes Mondo-Mlx controls a regulatory network composed of the Activin ligand Dawdle and GLI similar transcription factor Sugarbabe. Dawdle and Sugarbabe contribute to the regulation of a subset of Mondo-Mlx-dependent processes, including sugar-induced de novo synthesis of serine and fatty acids. In summary, our study establishes Mondo-Mlx sugar sensor as a master regulator of organismal metabolic homeostasis upon sugar feeding. Overall design: Control (sug17d/+) and sugarbabe null mutant (sug17d/sug def) third instar larvae were fed control low sugar or high sugar diet and total RNA was extracted from the whole larvae.
Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe.
Specimen part, Subject
View SamplesControl (+/cbtE1-UAS-cbt RNAi) or cabut RNAi flies (Tim-gal4, UAS-cbt RNAi) were starved for 16 hours and then exposed to food containing different concentrations of sucrose: 0, 25, 50 and 100 % for 18 hours. Fly heads were collected, RNA was extracted and RNA-seq libraries were prepared as previously described (Engreitz et al., 2013) Overall design: For each sucrose concentration, two samples of cabut RNAi flies and one sample of control flies were sequenced.
The transcription factor Cabut coordinates energy metabolism and the circadian clock in response to sugar sensing.
Specimen part, Subject
View Samples