This SuperSeries is composed of the SubSeries listed below.
Genomic profiling of CHEK2*1100delC-mutated breast carcinomas.
Specimen part
View SamplesIn order to identify relevant, molecularly defined subgroups in Multiple Myeloma (MM), gene expression profiling (GEP) was performed on purified CD138+ plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/ GMMG-HD4 trial using Affymetrix GeneChip U133 plus 2.0 arrays. Hierarchical clustering identified 10 distinct subgroups. Using this dataset as training data, a prognostic signature was built. The dataset consists of 282 CEL files previously used in the hierarchical clustering study of Broyl et al (Blood, 116(14):2543-53, 2010) outlined above. To this set 8 CEL-files/gene expression profiles were added. Using this set of 290 CEL-files, a prognostic signature of 92 genes (EMC-92-genesignature) was generated by supervised principal components analysis combined with simulated annealing (Kuiper et al.).
Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients.
Specimen part
View SamplesHistological classification of gliomas guides treatment decisions. Because of the high interobserver variability, we aimed to improve classification by performing gene expression profiling on a large cohort of glioma samples of all histological subtypes and grades. The seven identified intrinsic molecular subtypes are different from histological subgroups and correlate better to patient survival. Our data indicate that distinct molecular subgroups clearly benefit from treatment. Specific genetic changes (EGFR amplification, IDH1 mutation, 1p/19q LOH) segregate in -and may drive- the distinct molecular subgroups. Our findings were validated on three large independent sample cohorts (TCGA, REMBRANDT, and GSE12907). We provide compelling evidence that expression profiling is a more accurate and objective method to classify gliomas than histology.
Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer.
No sample metadata fields
View SamplesWe identified a tumor signature of 5 genes that aggregates the 156 tumor and normal samples into the expected groups. We also identified a histology signature of 75 genes, which classifies the samples in the major histological subtypes of NSCLC. A prognostic signature of 17 genes showed the best association with post-surgery survival time. The performance of the signatures was validated using a patient cohort of similar size
Gene expression-based classification of non-small cell lung carcinomas and survival prediction.
Sex, Specimen part
View SamplesCHEK2 1100delC is a moderate-risk cancer susceptibility allele that confers a high breast cancer risk in a polygenic setting. Gene expression profiling of CHEK2 1100delC breast cancers may reveal clues to the nature of the polygenic CHEK2 model and its genes involved. Here, we report global gene expression profiles of a cohort of 155 familial breast cancers, including 26 CHEK2 1100delC mutant tumors. A 40-gene CHEK2 signature was defined that significantly associated with CHEK2 1100delC breast cancers. The identification of a CHEK2 gene signature implies an unexpected biological homogeneity among the CHEK2 1100delC breast cancers. In addition, all 26 CHEK2 1100delC tumors classified as luminal intrinsic subtype breast cancers, with 8 luminal A and 18 luminal B tumors. This biological make-up of CHEK2 1100delC breast cancers suggests that a relatively limited number of additional susceptibility alleles are involved in the polygenic CHEK2 model. Identification of these as-yet-unknown susceptibility alleles should be aided by clues from the 40-gene CHEK2 signature.
Gene expression profiling assigns CHEK2 1100delC breast cancers to the luminal intrinsic subtypes.
Specimen part
View SamplesBreast cancer is a genetically and phenotypically complex disease. To understand the role of microRNAs in this molecular complexity, we performed miRNA expression analysis in a cohort of molecularly well-characterized human breast cancer (BC) cell lines to discover miRNAs associated with the most common molecular subtypes and the most frequent genetic aberrations.Using a microarray carrying LNA modified oligonucleotide capture probes (Exiqon), expression levels of 725 human miRNAs were measured in 51 BC cell lines. MiRNA expression was explored by unsupervised cluster analysis and then associated with the molecular subtypes and genetic aberrations commonly present in breast cancer. Unsupervised cluster analysis using the most variably expressed miRNAs divided the 51 BC cell lines into a major and a minor cluster predominantly mirroring the luminal and basal intrinsic subdivision of BC cell lines. One hundred and thirteen miRNAs were differentially expressed between these two main clusters of which half were related to the ER-status of the cell lines. Forty miRNAs were differentially expressed between basal-like and normal-like/claudin-low cell lines. Within the luminal-group of cell lines, 39 miRNAs were associated with ERBB2 overexpression and 24 miRNAs with E-cadherin gene mutations, which are frequent in this subtype of BC cell lines. In contrast, 31 different miRNAs were associated with E-cadherin promoter hypermethylation, which, contrary to E-cadherin mutation, is exclusively observed in BC cell lines that are not of luminal origin. The differential expression of 30 miRNAs were associated with p16INK4 status while only a few differentially expressed miRNAs were associated with BRCA1, or PIK3CA/PTEN, TP53 mutation status of the cell lines (P-value < 0.05). Twelve miRNAs were associated with DNA copy number variation of the respective locus. Luminal-basal and epithelial-mesenchymal associated miRNAs determine the overall subdivision of miRNA transcriptome of BC cell lines. Specific sets of miRNAs were associated with ERBB2 overexpression, p16INK4aor E-cadherin mutation or E-cadherin methylation status, which implies that these miRNAs may contribute to the driver role of the genetic aberrations. Additionally, miRNAs, which are located in a genomic region showing recurrent genetic aberrations, may themselves play a driver role in breast carcinogenesis or contribute to a driver gene in their vicinity. In short, our study provides detailed molecular miRNA portraits of BC cell lines, which can be exploited for functional studies of clinically important miRNAs.
miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs.
Cell line
View SamplesExpression data were used to predict the activity status of diverse pathways, which were compared to Tamoxifen response
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer.
No sample metadata fields
View SamplesThis 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 Samples