Microarray gene expression (MAGE) signatures allow insights into the transcriptional processes of leukemias and may evolve as a molecular diagnostic test. Introduction of MAGE into clinical practice of leukemia diagnosis will require comprehensive assessment of variation due to the methodologies.
New data on robustness of gene expression signatures in leukemia: comparison of three distinct total RNA preparation procedures.
No sample metadata fields
View SamplesRecently, it was described that mammalian cells are able to eliminate those with relative lower Myc levels in the epiblast through cell competition. We have described that cardiomyocytes during heart development are also able to complete eliminating cells with lower Myc levels. We have also shown that adult cardiomyocytes respond in the same way over long periods of time when cell competition is induced by overexpressing Myc in a mosaic fashion. We therefore have developed an RNASeq assay to further understand the mechanism of elimination of WT cells and the effect of mild Myc overexpression in cardiomyocytes. Overall design: Myc overexpression in a mosaic fashion in adult cardiomyocytes, 2 hearts were analyzed and two wild type littermates were used as controls
Cell competition promotes phenotypically silent cardiomyocyte replacement in the mammalian heart.
No sample metadata fields
View SamplesDespite advances in Hodgkin lymphoma (HL) treatment, about 20% of patients still die due to progressive disease. Current prognostic models predict treatment outcome with imperfect accuracy, and clinically relevant biomarkers are yet to be established that improve upon the International Prognostic Scoring (IPS) system. We analyzed 130 frozen diagnostic lymph node biopsies from classical HL patients by gene expression profiling to describe cellular signatures correlated with treatment outcome.
Tumor-associated macrophages and survival in classic Hodgkin's lymphoma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesWhsc1 gene codes for a SET domain-containing H3K36 dimethylase, whose activity has been suggested, in ex vivo cell culture experiments, to control many aspects of DNA and RNA processing (replication, repair, transcription, etc). Its precise function in vivo is still unclear. Here, we use RNA-seq transcriptome analysis to study the changes in gene expression in the absence of Whsc1. Our results show that, in the experimental system used, loss of Whsc1 caused massive changes in genes affecting many fundamental cellular processes, from cell cycle to ribosome synthesis, DNA repair, replication, etc. Overall design: Whsc1-KO mice are embryonic lethal. We therefore took hematopoietic cells from fetal liver of WT and Whsc1-KO embryo littermates and injected them in to lethally irradiated RAG1-KO recipients and allowed the generation of a full Whsc1-KO hematopoietic system. Then, WT and Whsc1-KO B cells were obtained from the spleen and stimulated with LPS to induce proliferation and class switch recombination. Flow cytometry and cell cycle analyses (among others) showed the existence of serious proliferative alterations in Whsc1-KO cells. Then, we performed paired-end RNAseq analyses of 7 independent WT and 6 independent Whsc1-KO biological replicates and we used these data to identify differentially expressed genes and pathways regulated by Whsc1 in B cells.
Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development.
Cell line, Subject
View SamplesThe genome of mantle cell lymphoma (MCL) is, in addition to the translocation t(11;14), characterized by a high number of secondary chromosomal gains and losses that likely account for the varying survival times of MCL patients. We investigated 77 primary MCL tumors with available clinical information using high resolution RNA expression and genomic profiling and applied our recently developed gene expression and dosage integrator (GEDI) algorithm to identify novel genes and pathways that may be of relevance for the pathobiology of MCL. We show that copy number neutral loss of heterozygosity (CNN-LOH) is common in MCL and targets regions that are frequently affected by deletions. The molecular consequences of genomic copy number changes appear complex, even in genomic loci with identified tumor suppressors, such as the region 9p21 containing the CDKN2A locus. Moreover, the deregulation of novel genes such as CUL4A, ING1 and MCPH1 may affect the two crucial pathogenetic mechanisms in MCL, the disturbance of the proliferation and DNA damage response pathways. Deregulation of the Hippo pathway may have a pathogenetic role in MCL, since decreased expression of its members MOBKL2A, MOBKL2B and LATS2 was associated with inferior outcome also in an independent validation series of 32 MCL.
Pathway discovery in mantle cell lymphoma by integrated analysis of high-resolution gene expression and copy number profiling.
Disease, Disease stage, Subject
View SamplesFollicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied regarding their immunohistochemical, genetic, molecular and clinical features. Within a previously published series of 184 FL grade 1-3A with available gene expression data, we identified 17 FL lacking the t(14;18). Comparative genomic hybridization and high resolution SNP array profiling demonstrated that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles revealed an enrichment of germinal center B-cell associated signatures in t(14;18)-positive FL, whereas activated B-cell like, NFB, proliferation and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FL, in which 32% of t(14;18)-negative FL showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.
Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations.
Specimen part, Disease, Disease stage, Subject
View SamplesThe assignment of diffuse large B-cell lymphoma into cell-of-origin (COO) groups is becoming increasingly important with the emergence of novel therapies that have selective biological activity in germinal center B-cell-like (GCB) or activated B-cell-like (ABC) groups. The LLMPP's Lymph2Cx assay is a parsimonious digital gene-expression (NanoString) based test for COO assignment in formalin-fixed paraffin-embedded tissue (FFPET) routinely produced in standard diagnostic processes. The 20-gene assay was trained using 51 FFPET biopsies; the locked assay was then validated using an independent cohort of 68 FFPET biopsies. Comparisons were made with COO assignment using the original COO model on matched frozen tissue. In the validation cohort the assay was accurate, with only one case with definitive COO being incorrectly assigned, and robust, with >95% concordance of COO assignment between 2 independent laboratories. These qualities, along with the rapid turn-around-time, make Lymph2Cx attractive for implementation in clinical trials and, ultimately, patient management.
Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesGlioblastomas (GBM) are one of the most frequent and aggressive brain tumors. In these malignancies, progesterone (P4) promotes proliferation, migration, and invasion. The P4 metabolite allopregnanolone (3-THP) similarly promotes cell proliferation in the U87 human GBM cell line.
Allopregnanolone Alters the Gene Expression Profile of Human Glioblastoma Cells.
Specimen part, Cell line, Treatment
View SamplesWe performed array comparative genomic hybridization (aCGH) and gene expression profiling in 203 samples of diffuse large B cell lymphoma (DLBCL). By gene expression, at least three molecular subtypes of DLBCL termed as germinal center B cell-like (GCB) DLBCL, activated B cell-like (ABC) DLBCL, and primary mediastinal B cell lymphoma (PMBL) can be distinguished. Combining gene expression profiling and aCGH, revealed copy number abnormalities that had strikingly different frequencies in the three molecular DLBCL subtypes. These data provide genetic evidence that the DLBCL subtypes are distinct diseases that utilize different oncogenic pathways.
Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide copy-number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma.
No sample metadata fields
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