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GSE104099
Homo sapiens
43 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression in NPM1 wildtype and mutated AML patients with high or low hsa_circ_0075001 expression
Publication Title
Circular RNAs of the nucleophosmin (NPM1) gene in acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute myeloid leukemia (AML) is characterized by molecular heterogeneity. As commonly altered genomic regions point to candidate genes involved in leukemogenesis, we used microarray-based comparative genomic hybridization and single nucleotide polymorphism profiling data of 391 AML cases to further narrow down genomic regions of interest. Targeted-resequencing of 1000 genes located in the critical regions was performed in a representative cohort of 50 AML samples comprising all major cytogenetic subgroups. We identified 120 missense/nonsense mutations as well as 60 insertions/deletions affecting 73 different genes (~3.6 tumor-specific aberrations/AML). While most of the newly identified alterations were non-recurrent, we observed a number of mutations affecting genes involved in epigenetic regulation including known candidates like TET2, TET1, DNMT3A and DNMT1, as well as mutations in the histone methyltransferases NSD1, EZH2 and MLL3. Furthermore, we found mutations in the splicing factor SFPQ and in the non-classical regulators of mRNA-processing CTCF and RAD21. These splicing-related mutations affected 10% of AML patients in a mutually exclusive manner. In conclusion, we could identify a significant enrichment of alterations in genes involved in aberrant splicing and epigenetic regulation in genomic regions commonly altered in AML, highlighting their important role in the molecular pathogenesis of AML.
Publication Title
Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Acute myeloid leukemia (AML) is driven by somatic mutations and genomic rearrangements affecting >20 genes. Many of these are recent discoveries and how this molecular heterogeneity dictates AML pathophysiology and clinical outcome remains unclear. Methods: We sequenced 111 leukemia genes for driver mutations in 1540 AML patients with cytogenetic and clinical data. We modeled AMLs genomic structure, defining genetic interactions, patterns of temporal evolution and clinical correlations. Results: We identified 5,236 driver mutations involving 77 loci, including hotspot mutations in MYC. We found 1 driver mutation in 96% patients, and 2 in 85%. Gene mutations implicated in age related clonal hematopoiesis (DNMT3A, ASXL1, TET2) were the earliest in AML evolution, followed by highly specific and ordered patterns of co-mutation in chromatin, transcription and splicing regulators, NPM1 and signaling genes. The patterns of co-mutation compartmentalize AML into 12 discrete molecular classes, each presenting with distinct clinical manifestation. Amongst these, mutations in chromatin and spliceosome genes demarcate a molecularly heterogeneous subgroup enriched for older AML patients currently classified as intermediate risk and results in adverse prognosis. Two- and three-way genetic interactions often implicating rare genes/mutation-hotspots, markedly redefined clinical response and long-term curability, with the NPM1:DNMT3A:FLT3ITD genotype (6% patients) identifying poor prognosis disease, whereas within the same class NPM1:DNMT3A:NRASG12/13 (3%) associated with favorable outlooks. Conclusions: 79% of AML is molecularly classified in 12 genomic subgroups. These represent distinct molecular phylogenies, implicating complex genotypes. Delineation of higher-order genomic relationships, guide the development of personally tailored classification, prognostication and clinical protocols. Similar studies across cancer types are warranted.
Publication Title
Genomic Classification and Prognosis in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part, Disease
View Samples- Caenorhabditis elegans
- 52 Downloadable Samples
Illumina HiSeq 2000
Description
We report the presence of extensive, transcriptionally controlled oscillations in the C. elegans, developmental transcriptome. Furthermore, using ribosome profiling, we show that these oscillating transcripts are actively translated. Overall design: Examination of three timecourses that were collected over C. elegans development and analyzed by RNA-seq of mRNA libraries
Publication Title
Extensive oscillatory gene expression during C. elegans larval development.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 34 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the presence of extensive, transcriptionally controlled oscillations in the C. elegans, developmental transcriptome. Furthermore, using ribosome profiling, we show that these oscillating transcripts are actively translated. Overall design: Examination of two timecourses that were collected over C. elegans development and analyzed by RNA-seq of "RiboMinus" libraries
Publication Title
Extensive oscillatory gene expression during C. elegans larval development.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Relative contribution of sequence and structural features to the mRNA-binding of Argonaute/miRNA complexes and the degradation of miRNA targets
Publication Title
Relative contribution of sequence and structure features to the mRNA binding of Argonaute/EIF2C-miRNA complexes and the degradation of miRNA targets.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
microRNAs (miRNAs) constitute a class of small non-coding RNAs (~22nt). They are thought to be generally stable with half-lives of many hours or even days. However, several miRNAs have been reported to decay rapidly in specific situations. In order to examine miRNA stability on a global scale, we quantify relative decay rates of miRNA in first larval stage C. elegans worms that are treated with a transcription inhibitor alpha-amanitin by deep sequencing. Several miRNAs including members of the miR-35 and miR-51 families exhibit accelerated decay. Moreover, biogenesis of miRNAs involves generation of a miRNA duplex intermediate consisting of the miRNA guide strand (miR) and the miRNA passenger strand (miR*). miR and miR* names were originally assigned based on the relative abundance of each strand, with the less abundant strand presumed to be inactive, and thus the miR*. However, subsequent research showed that at least individual miR*s can have biological activity. Our sequencing data reveal that miR*s, operationally defined on the basis of their relative abundance at time point t=1h, are substantially less stable than miRs. This would appear to support the notion that miR*s mainly constitute processing byproducts rather than a less abundant class of functional miRNAs. Overall design: Examination of microRNA decay rates in the first larval stage C. elegans worms.
Publication Title
Engineering of a conditional allele reveals multiple roles of XRN2 in Caenorhabditis elegans development and substrate specificity in microRNA turnover.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We identify mammalian TRIM71 as repressor of mRNAs that inhibits translation and affects mRNA stability.
Publication Title
The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We identify mammalian TRIM71 as repressor of mRNAs that inhibits translation and affects mRNA stability. In this data set we compare the expression profile of mouse ES upon Trim71 KD versus that of the parental cells.
Publication Title
The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function.
Sample Metadata Fields
Specimen part
View Samples