Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393006 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5802590_1.fastq.gz | Fastqsanger.gz | |||
| SRR5802590_2.fastq.gz | Fastqsanger.gz | |||
| SRR5802600_1.fastq.gz | Fastqsanger.gz | |||
| SRR5802600_2.fastq.gz | Fastqsanger.gz | |||
| SRR5802610_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:We identified novel recurrent genetic lesions in T-PLL affecting genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, HERC2). Mutations of the tumor suppressor gene SAMHD1 causing amino-acid exchanges or protein truncations as well as copy number variations in SAMHD1 were seen in 20% of cases.
2018-07-23 | GSE100844 | GEO
Project description:We identified novel recurrent genetic lesions in T-PLL affecting genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, HERC2). Mutations of the tumor suppressor gene SAMHD1 causing amino-acid exchanges or protein truncations as well as copy number variations in SAMHD1 were seen in 20% of cases.
2018-02-22 | GSE100882 | GEO
Project description:T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm with aggressive clinical course and short overall survival. So far, due to the rareness of this disease, genetic data is available only from individual cases or small cohorts. In our study, we aimed at performing a comprehensive cytogenetic and molecular genetic characterization of T-PLL comprising the largest cohort of patients with T-PLL analyzed so far, including correlations between the respective markers and their impact on prognosis. Genetic abnormalities were found in all 51 cases with T-PLL, most frequently involving the TCRA/D locus (86%). Deletions were detected for ATM (69%) and TP53 (31%), whereas i(8)(q10) was observed in 61% of cases. Mutations in ATM, TP53, JAK1 and JAK3 were detected in 73%, 14%, 6%, and 21% of patients, respectively. Additionally, BCOR mutations were observed for the first time in a lymphoid malignancy (8%). Two distinct genetic subgroups of T-PLL were identified: A large subset (86% of patients) showed abnormalities involving the TCRA/D locus activating the proto-oncogenes TCL1 or MTCP1, while the second group was characterized by a high frequency of TP53 mutations (4/7 cases). Further, analyses of overall survival identified JAK3 mutations as important prognostic marker, showing a significant negative impact.
2015-02-05 | GSE65649 | GEO
Project description:The recognition of B-cell prolymphocytic leukemia (B-PLL) as a separate entity is controversial based on the current classification systems. Here, we analyze the DNA methylome of a cohort of 20 B-PLL cases diagnosed according to the ICC/WHO-HAEM4R guidelines, and compare them with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and normal B cell subpopulations. Unsupervised principal component analyses suggest that B-PLL is epigenetically distinct from CLL, MCL and SMZL, which is further supported by robust differential methylation signatures in B-PLL. We also observe that B-PLL can be segregated into two epitypes with differential clinico-biological characteristics. B-PLL epitype 1 carries lower IGHV somatic hypermutation and a less profound germinal center-related DNA methylation imprint than epitype 2. Furthermore, epitype 1 is significantly enriched in mutations affecting MYC and SF3B1 as well as gain 1q, and displays DNA hypomethylation and gene upregulation signatures enriched in MYC targets. Despite the low sample size, patients from epitype 1 have an inferior overall survival than those of epitype 2. This study provides relevant insights into the biology and differential diagnosis of B-PLL, and potentially identifies two subgroups with distinct biological and clinical features.
2025-01-08 | GSE279602 | GEO
Project description:In mammalian cells, the catabolic activity of the dNTP triphosphohydrolase SAMHD1 sets the balance and the concentrations of the four dNTPs. Deficiency of SAMHD1 leads to unequally increased pools and marked dNTP imbalance. Although it is documented that imbalanced dNTP pool expansion increases mutation frequency in cancer cells, it is not known if the SAMHD1-induced dNTP imbalance favors accumulation of somatic mutations in non-transformed cells. Here we have investigated how fibroblasts isolated from Aicardi Goutières Syndrome (AGS) patients with mutated SAMHD1 react to the constitutive pool imbalance characterized by a huge dGTP pool. We focused on the effects on dNTP pools, cell-cycle progression, dynamics and fidelity of DNA replication, efficiency of UV-induced DNA repair. AGS fibroblasts entered senescence prematurely or upregulated genes involved in G1/S transition and DNA replication. The normally growing AGS cells exhibited unchanged DNA replication dynamics and, when quiescent, faster rate of excision repair of UV-induced DNA damages than wildtype fibroblasts. To investigate if the lack of SAMHD1 affects DNA replication fidelity we compared de novo mutations in AGS and WT cells by exome next generation sequencing. Somatic variant analysis indicated a mutator phenotype suggesting that SAMHD1 is a caretaker gene whose deficiency is per se mutagenic promoting genome instability in non-transformed cells.
2019-12-03 | GSE135652 | GEO
Project description:T cell prolymphocytic leukemia (T-PLL) is mostly characterized by aberrant expansion of small to medium sized pro-lymphocytes with a mature post-thymic phenotype, high aggressiveness of the disease and poor prognosis. However, T-PLL is more heterogeneous with a wide-range of clinical, morphological, and molecular features, which occasionally impedes the diagnosis. We hypothesized that T-PLL consists of phenotypic and genotypic subgroups that may explain the heterogeneity of the disease. We found that T-PLL does not show a clear skewing in T cell receptor alpha (TRA), TRB gene usage and CDR3 stereotypy. In addition, multi-dimensional immuno-phenotyping and gene expression profiling did not reveal clear T-PLL subgroups. However, based on miRNA expression profiles, T-PLL samples did clearly cluster in subgroups. We identified 35 miRNAs that were aberrantly expressed in T-PLL with miR-200c/141 as the most differentially expressed cluster. High miR-200c/141 expression was significantly correlated with increased white blood cell counts and poor survival. Furthermore, we found that overexpression of miR-200c/141 in T-PLL correlated with downregulation of their targets ZEB2 and TGFβR3, indicating that the TGFβ pathway is affected. Our results thus highlight the emerging role for aberrantly expressed oncogenic miRNAs in T-PLL, thereby paving the way for new therapeutic targets in this disease.
2021-04-02 | GSE147932 | GEO
Project description:T-cell prolymphocytic leukemia (T-PLL) is a rare disease with rapid clinical course. Whole-exome and whole-genome sequencing have identified structural alterations in T-PLL, including inversion, translocation and copy number variation. Epigenetic alterations are the hallmark of many cancers. However, genome-wide epigenomic profiles have not been reported in T-PLL. In this study, we generated genome-wide maps of regulatory regions in both T-PLL patients and healthy individuals using H3K4me3 and H3K27ac ChIP-seq. We revealed a global alteration of both promoter and enhancer landscape in T-PLL, which supported the role of epigenetic regulation in transcriptional dysregulation of oncogenes and genes involved in DNA damage response and T-cell activation.
2021-04-20 | GSE143374 | GEO
Project description:SAMHD1 restricts HIV-1 replication in dendritic and other myeloid cells. SAMHD1 has been shown to possess a dGTP-dependent dNTP triphosphatase (dNTPase) activity and is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool. Arguing against a role for SAMHD1 dNTPase in HIV-1 restriction, the phosphorylation of SAMHD1 regulates the restriction activity toward HIV-1 without affecting its ability to decrease cellular dNTP levels. Here, we show that SAMHD1 is a phospho-regulated RNase and that the RNase function is required for HIV-1 restriction. Mutation of the SAMHD1 D137 residue in the allosteric site (SAMHD1D137N) abolishes dNTPase activity but has no effect on RNase activity. This dNTPase-defective SAMHD1D137N mutant is able to restrict HIV-1 infection to nearly the same extent as wild-type SAMHD1. SAMHD1 associates with and degrades the HIV-1 genomic RNA during the early phases of infection. SAMHD1 silencing in macrophages and CD4+ T cells from healthy donors increases HIV-1 RNA stability, thus rendering the cells permissive for HIV-1 infection. Furthermore, the phosphorylation of SAMHD1 at position T592 abolishes the RNase activity toward HIV-1 RNA, and consequently the ability of SAMHD1 to restrict HIV-1 infection, uncovering the phosphorylation of SAMHD1 T592 as a negative regulatory mechanism of RNase activity. Together, our results demonstrate that SAMHD1 is an essential RNase that prevents HIV-1 infection by directly degrading HIV-1 genomic RNA in a phosphorylation-regulated manner. The unique property of SAMHD1 that cleaves HIV-1 genomic RNA with no sequence preferences could be exploited to develop a new class of intervention for error-prone retroviruses. Ribosomal RNA-depleted total RNA profiles of mock, SAMHD1 wild type and mutants infected with HIV-1 were examined at the time of 0, 1, 3 h by Illumina Hiseq2500.
2014-06-13 | E-GEOD-58418 | biostudies-arrayexpress
Project description:To investigate the contribution of type-1 IFN signalling to the upregulation of IFN- stimulated genes in SAMHD1-deficient cells, we performed global gene expression analysis of SAMHD1-deficient IFNAR-/- macrophages. Peritoneal macrophages from ten SAMHD1-deficient IFNAR-/- and six SAMHD1-deficient controls were FACS sorted. RNA was subjected to next generation mRNA sequencing.
2013-07-01 | E-GEOD-45358 | biostudies-arrayexpress
Project description:We evaluated 13 B-PLL patient, 7 of whom were t(11;14)-positive (B-PLL+), and compared them with MCL and CLL patients.
2014-05-29 | E-MTAB-1991 | biostudies-arrayexpress