Project description:In 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 Gene Chip U133 plus 2.0 arrays. Hierarchical clustering identified 10 distinct subgroups. Bone marrow plasma cell samples were obtained from 320 newly diagnosed multiple myeloma patients included in a large multicenter, prospective, randomized phase III trial (HOVON65/GMMG-HD4). Purified myeloma plasma cells samples with a monoclonal plasma cell purity > 80% were used for analysis.
Project description:Multiple myeloma is a relatively common B-cell malignancy that is currently incurable. Certain recurrent genetic abnormalities characteristics of different genetic subtypes have been described. Hyperdiploid myeloma characterized by recurrent trisomies is the most common genetic subtypes. However little is know about it's biology. Another common genetic abnormality is chromosome 13 deletion which is also associated with inferior prognosis. This abnormality is already present at the pre-malignant MGUS stage and is clonally selected with disease progression. Although it is biologically and clinically important the molecular consequence of chromosome 13 deletion is unknown. Experiment Overall Design: Hyperdiploid myeloma was identified using FISH. The gene expression profile of hyperdiploid MM is compared to that of non-hyperdiploid myeloma to identify differentially expressed genes. Molecular heterogeneity within H-MM is analyzed using unsupervised techniques. The distinctive subgroups identified are also tested in MGUS/SMM and NH-MM. The clinical relevance of these subtypes of hyperdiploid myeloma is then analyzed by correlating with relevant clinical information. Chromosome 13 deleted and undeleted MM are identified by FISH and their gene expression profile compared to identify molecular signature.
Project description:Analysis of mechano-regulation of eIF2α phosphatases in multiple myeloma cells at gene expression level. The hypothesis tested in the present study was Guanbenz (GBZ) and Sal003, 2 different eIF2α phosphatases induce different responses in multiple myeloma cells . Results provide important information of the responses of multiple myeloma cells, such as specific mechano-responsive genes, up- or down-regulated specific cellular functions
Project description:In 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.).
Project description:Multiple myeloma (MM) is a clonal plasma cell disorder frequently accompanied by hematopoietic impairment. Genomic profiling of distinct HSPC subsets revealed a consistent deregulation of signaling cascades, including TGF beta signaling, p38MAPK signaling and pathways involved in cytoskeletal organization, migration, adhesion and cell cycle regulation in MM patients. CD34+ subsets of 7 patients with Multiple Myeloma and 5 healthy volunteers were analysed by means of gene expression profiling with the Affymetrix HU-133A 2.0 array
Project description:To characterize DNA methylation-based subgroups in colorectal cancer, we performed genome-scale DNA methylation profiling of 125 colorectal tumor samples and 29 histologically normal-adjacent colonic tissue samples using the Illumina Infinium DNA methylation assay, which assesses the DNA methylation status of 27,578 CpG sites located at the promoter regions of 14,495 protein-coding genes. We identified four DNA methylation-based subgroups of CRC using model-based cluster analyses. Each subtype shows characteristic genetic and clinical features, indicating that they represent biologically distinct subgroups.
Project description:We combined mRNA, small RNA and ribosome methylation sequencing to investigate snoRNA expression patterns in multiple myeloma and their association with different chromosomal aberrations. We identified snoRNAs dysregulated in molecular subgroups, with SNORD78 being highly expressed in gain1q patients and associated with poor prognosis. Our study shows that the expression of particular snoRNAs and methylation of specific snoRNA-guided rRNA sites are associated with specific chromosome gains, which are common elements in multiple myeloma.
