Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA126151 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Global alternative splicing in patients with acute myeloid leukemia
| PRJNA921731 | ENA
Project description:Global mRNA alternative splicing in patients with acute myeloid leukemia
| PRJNA924552 | ENA
Project description:Alternative mRNA splicing represents an effective mechanism of regulating gene function and is a key element to increase the coding capacity of the human genome. Today, an increasing number of reports illustrates that aberrant splicing events are common and functionally important for cancer development. However, more comprehensive analyses are warranted to get novel insights into the biology underlying malignancies like e.g. acute myeloid leukemia (AML). Here, we performed a genome-wide screening of splicing events in AML using an exon microarray platform. We analyzed complex karyotype and core binding factor (CBF) AML cases (n=64) in order to evaluate the ability to detect alternative splicing events distinguishing distinct leukemia subgroups. Testing different commercial and open source software tools to compare the respective AML subgroups, we could identify a large number of potentially alternatively spliced transcripts with a certain overlap of the different approaches. Selected candidates were further investigated by PCR and sequence analysis: out of 24 candidate genes studied, we could confirm alternative splice forms in 8 genes of potential pathogenic relevance, such as PRMT1 regulating transcription through histone methylation and participating in DNA damage response, and PTPN6, which encodes for a negative regulator of cell cycle control and apoptosis. In summary, this first large Exon microarray based study demonstrates that transcriptome splicing analysis in AML is feasible but challenging, in particular with regard to the currently available software solutions. Nevertheless, our results show that alternatively spliced candidate genes can be detected, and we provide a guide how to approach such analyses. Exon expression analysis was performed using GeneChip Human Exon 1.0 ST microarrays in 64 AML patients.
2014-12-15 | E-GEOD-21337 | biostudies-arrayexpress
Project description:Transcription start sites are the focal points of transcriptional regulation, where information from regulatory elements is integrated to stabilize initiation of transcription. In humans, most genes have more than one transcription start site, and these often exhibit different tissue specificity, serving as distinct regulatory frameworks for the same gene. Usage of such promoters can also result in differential gene function manifested on the protein level. Alternative promoter usage has been shown to be increased in several disease states, especially cancer. In this study, we have applied the nanoCAGE method to create a genome-wide map of TSS usage in sorted leukemic blasts from acute myeloid leukemia patients, and corresponding normal controls. We show that the nanoCAGE method can replace similar experiments made with microarrays in terms of expression, but also that it uniquely, allow for the identification of alternative promoter usage in cancer cells. We identify 2,162 putative promoters that are significantly differentially regulated between APL and controls. Interestingly, promoters whose usage is upregulated in APL have an increased propensity to be downstream alternative promoters, and conversely, the promoters producing the annotated longest gene variants are commonly downregulated in cancer. We show examples of genes with upregulated downstream promoters, and demonstrate protein domain loss that could contribute to leukemic induction and maintenance. In conclusion, we present the first genome wide promoterome study from rare purified human leukemic cells. nanoCAGE-seq of human acute myeloid leukemia samples vs. normal hematopoietic counterparts, both in replicates
2014-01-31 | E-GEOD-46561 | biostudies-arrayexpress
Project description:Mutations in isocitrate dehydrogenase 2 (IDH2) occur in many cancers including Acute Myeloid Leukemia (AML). Recently, we showed that single agent Enasidenib, a first-in-class, selective mutant IDH2 inhibitor, produces a 40% response in relapsed/refractory AML patients by promoting differentiation of leukaemic cells. In this current study, we describe two patients who responded to Enasidenib treatment but subsequently relapsed with an IDH2-mutant subclone which had acquired mutations in DHX15 and DDX1 genes. These genes have putative functions in regulating splicing. We have studied the alternative splicing events using RNASeq in the sample pre-relapse (before acquisition of DHX15 and DDX1 mutations) and at relapse (after acquisition of DHX15 and DDX1 mutations).
2018-08-08 | E-MTAB-6660 | biostudies-arrayexpress
Project description:Alternative mRNA splicing represents an effective mechanism of regulating gene function and is a key element to increase the coding capacity of the human genome. Today, an increasing number of reports illustrates that aberrant splicing events are common and functionally important for cancer development. However, more comprehensive analyses are warranted to get novel insights into the biology underlying malignancies like e.g. acute myeloid leukemia (AML). Here, we performed a genome-wide screening of splicing events in AML using an exon microarray platform. We analyzed complex karyotype and core binding factor (CBF) AML cases (n=64) in order to evaluate the ability to detect alternative splicing events distinguishing distinct leukemia subgroups. Testing different commercial and open source software tools to compare the respective AML subgroups, we could identify a large number of potentially alternatively spliced transcripts with a certain overlap of the different approaches. Selected candidates were further investigated by PCR and sequence analysis: out of 24 candidate genes studied, we could confirm alternative splice forms in 8 genes of potential pathogenic relevance, such as PRMT1 regulating transcription through histone methylation and participating in DNA damage response, and PTPN6, which encodes for a negative regulator of cell cycle control and apoptosis. In summary, this first large Exon microarray based study demonstrates that transcriptome splicing analysis in AML is feasible but challenging, in particular with regard to the currently available software solutions. Nevertheless, our results show that alternatively spliced candidate genes can be detected, and we provide a guide how to approach such analyses.
2014-12-15 | GSE21337 | GEO
Project description:A novel NUP98/RARG gene fusion in acute myeloid leukemia resembling acute promyelocytic leukemia
2010-10-18 | E-MEXP-2928 | biostudies-arrayexpress
Project description:Splicing Variation Contributes to Functional Dysregulation of Genes in Acute Myeloid Leukemia
| PRJNA597243 | ENA
Project description:Acute Myeloid Leukemia (AML) has been associated with somatic mutations in numerous genes; however, the penetrance of these mutations is low. Here we investigate the contribution of alternative splicing as an additional layer of gene dysregulation in AML. By analyzing splicing variations across two patient datasets, we find a consistent set of splicing events that disrupt the coding potential of a subset of AML-associated genes. Importantly, most of these splicing variations are independent of any currently-identified somatic mutations. We have further validated that for EZH2 and ZRSR2 these splicing events reduce the expression of full-length protein. Together these results highlight the contribution of splicing to gene dysregulation and demonstrate that mutation analysis underestimates the burden of functional gene disruption in patient populations.
2021-04-01 | GSE142514 | GEO