Similar Datasets
Project description:Combination analysis of m6A-seq, IGF2BP1-KD RNA-seq, IGF2BP1 CLIP-seq in H929 cells
2024-05-31 | GSE202974 | GEO
Project description:Combination analysis of m6A-seq, IGF2BP1-KD RNA-seq, IGF2BP1 CLIP-seq in H929 cells
2024-05-31 | GSE202973 | GEO
Project description:Background: Gain and/or amplification of chromosome 1q are frequently found in Multiple Myeloma (MM). The number of 1q copies correlates with a poor prognosis. The aim of this work is to study the impact on the clinical outcome and the trascriptomic changes induced by Gain1q (3 copies of 1q, 3X) and amplification 1q (Amp1q, ≥4 copies of 1q, 4X) in MM patients enrolled in the CoMMpass study (NCT145429). Methods: Fluorescence in situ hybridization (FISH) in CD138+ purified bone marrow plasma cells was centralized and performed at baseline. The cut-off level for Gain1q was 10% of nuclei with ≥3 copies of 1q (3X), while Amp1q was defined as ≥ 20% of nuclei with ≥4 copies of 1q (4X). Transcriptome data from patients were used to find differentially expressed genes (DEGs) in gain (3X) and amp1q (4X) patients.
2023-01-16 | GSE193427 | GEO
Project description:Gain of chromosome 1q (+1q) is commonly identified in multiple myeloma and has been associated with inferior outcomes. However, the prognostic implication of +1q has not been evaluated in the setting of standard triplet regimens. We retrospectively analyzed 201 consecutive patients with newly diagnosed myeloma who received induction with lenalidomide, bortezomib, and dexamethasone (RVD) and were tested for +1q at diagnosis by fluorescent in-situ hybridization. Patients with +1q (n?=?94), compared to those without +1q (n?=?107), had shorter median progression-free survival (PFS) (41.9 months vs 65.1 months, p?=?0.002, HR?=?1.90) and overall survival (median not reached (NR) for either arm, p?=?0.003, HR 2.69). In subgroup analyses, patients with co-occurring +1q and t(4;14), t(14;16) or del(17p) or with 4 or more copies of 1q had significantly worse PFS (25.1 months and 34.6 months, p?<?0.001 and p?=?0.0063, respectively), whereas patients with three copies and no other high-risk cytogenetic abnormalities had no significant difference in PFS. These data suggest that when treated with RVD induction, patients with +1q should be considered at very high risk for early progression in multiple myeloma when ?4 copies are detected or in the context of other high-risk cytogenetic abnormalities.
| S-EPMC6877577 | biostudies-literature
Project description:Patients with multiple myeloma (MM) accumulate adverse copy number aberrations (CNAs), gains of 1q21, and 17p deletions during disease progression. A subset of these patients develops heightened 1q12 pericentromeric instability and jumping translocations of 1q12 (JT1q12), evidenced by increased copy CNAs of 1q21 and losses in receptor chromosomes (RC). To understand the progression of these aberrations we analyzed metaphase cells of 50 patients with ≥4 CNAs of 1q21 by G-banding, locus specific FISH, and spectral karyotyping. In eight patients with ≥5 CNAs of 1q21 we identified a chromosome instability phenotype similar to that found in ICF syndrome (immunodeficiency, centromeric instability, and facial anomalies). Strikingly, the acquired instability phenotype identified in these patients demonstrates the same transient structural aberrations of 1q12 as those found in ICF syndrome, suggesting similar underlying pathological mechanisms. Four types of clonal aberrations characterize this phenotype including JT1q12s, RC deletions, 1q12-21 breakage-fusion-bridge cycle amplifications, and RC insertions. In addition, recurring transient aberrations include 1q12 decondensation and breakage, triradials, and 1q micronuclei. The acquired self-propagating mobile property of 1q12 satellite DNA drives the continuous regeneration of 1q12 duplication/deletion events. For patients demonstrating this instability phenotype, we propose the term "Jumping 1q Syndrome."
| S-EPMC6689064 | biostudies-literature
Project description:A gain in chromosome 1q (+1q) is among the most common cytogenetic abnormalities in multiple myeloma (MM). It is unclear whether +1q is independently associated with decreased overall survival (OS). The objective of this study was to evaluate the impact of +1q on clinical characteristics, treatment response, and survival outcomes. We included 1376 Mayo Clinic patients diagnosed with MM from 2005 to 2018 who underwent fluorescence in situ hybridization testing at diagnosis with a panel including the +1q probe. A gain in 1q was found in 391 patients (28%) and was associated with anemia, hypercalcemia, high tumor burden, International Staging System (ISS) stage 3, high-risk (HR) translocations, and chromosome 13 abnormalities. There was no difference in overall response or deeper responses to proteasome inhibitor (PI)-, immunomodulatory drug (iMiD)-, or PI plus IMiD-based induction. Time to next treatment was shorter in patients with +1q compared with those without +1q (19.9 vs 27.7 months; P < .001). On univariate analysis, +1q was associated with increased risk of death (risk ratio [RR], 1.9; P < .001), and decreased OS was seen in all treatment groups. +1q was independently associated with decreased OS on multivariate analysis when other HR cytogenetic abnormalities, ISS stage 3, and age ≥70 years were included (RR, 1.5; P < .001). Gain of >1 copy of 1q was not associated with worse OS compared with gain of 1 copy (4.9 vs 4.3 years; P = .21). +1q was associated with high tumor burden, advanced disease stage, and HR translocations. It is independently associated with decreased OS, even in the setting of novel therapy and transplant.
| S-EPMC7422105 | biostudies-literature
Project description:Multiple myeloma (MM), a plasma cell neoplasm, is an incurable hematological malignancy characterized by complex genetic and prognostic heterogeneity. Gain or amplification of chromosome arm 1q21 (1q21+) is the most frequent adverse chromosomal aberration in MM, occurring in 40% of patients at diagnosis. It occurs in a subclone of the tumor as a secondary genomic event and is more amplified as the tumor progresses and a risk factor for the progression from smoldering multiple myeloma to MM. It can be divided into either 1q21 gain (3 copies) or 1q21 amplification (?4 copies), and it has been suggested that the prognosis is worse in cases of amplification than gain. Trisomy of chromosome 1, jumping whole-arm translocations of chromosome1q, and tandem duplications lead to 1q21+ suggesting that its occurrence is not consistent at the genomic level. Many studies have reported that genes associated with the malignant phenotype of MM are situated on the 1q21 amplicon, including CKS1B, PSMD4, MCL1, ANP32E, and others. In this paper, we review the current knowledge regarding the clinical features, prognostic implications, and the speculated pathology of 1q21+ in MM, which can provide clues for an effective treatment approach to MM patients with 1q21+.
| S-EPMC7827173 | biostudies-literature
Project description:BackgroundEpendymomas account for up to 10% of childhood CNS tumors and have a high rate of tumor recurrence despite gross total resection. Recently, classification into molecular ependymoma subgroups has been established, but the mechanisms underlying the aggressiveness of certain subtypes remain widely enigmatic. The aim of this study was to dissect the clinical and biological role of telomerase reactivation, a frequent mechanism of cancer cells to evade cellular senescence, in pediatric ependymoma.MethodsWe determined telomerase enzymatic activity, hTERT mRNA expression, promoter methylation, and the rs2853669 single nucleotide polymorphism located in the hTERT promoter in a well-characterized cohort of pediatric intracranial ependymomas.ResultsIn posterior fossa ependymoma group A (PF-EPN-A) tumors, telomerase activity varied and was significantly associated with dismal overall survival, whereas telomerase reactivation was present in all supratentorial RelA fusion-positive (ST-EPN-RELA) ependymomas. In silico analysis of methylation patterns showed that only these two subgroups harbor hypermethylated hTERT promoters suggesting telomerase reactivation via epigenetic mechanisms. Furthermore, chromosome 1q gain, a well-known negative prognostic factor, was strongly associated with telomerase reactivation in PF-EPN-A. Additional in silico analyses of gene expression data confirmed this finding and further showed enrichment of the E-twenty-six factor, Myc, and E2F target genes in 1q gained ependymomas. Additionally, 1q gained tumors showed elevated expression of ETV3, an E-twenty-six factor gene located on chromosome 1q.ConclusionTaken together we describe a subgroup-specific impact of telomerase reactivation on disease progression in pediatric ependymoma and provide preliminary evidence for the involved molecular mechanisms.
| S-EPMC5570194 | biostudies-literature
Project description:Ependymoma (EPN) is a common brain tumor of childhood that, despite standard surgery and radiation therapy, has a relapse rate of 50%. Clinical trials have been unsuccessful in improving outcome by addition of chemotherapy, and identification of novel therapeutics has been hampered by a lack of in vitro and in vivo models. We describe 2 unique EPN cell lines (811 and 928) derived from recurrent intracranial metastases. Both cell lines harbor the high-risk chromosome 1q gain (1q+) and a derivative chromosome 6, and both are classified as molecular group A according to transcriptomic analysis. Transcriptional enrichment of extracellular matrix-related genes was a common signature of corresponding primary tumors and cell lines in both monolayer and 3D formats. EPN cell lines, when cultured in 3D format, clustered closer to the primary tumors with better fidelity of EPN-specific transcripts than when grown as a monolayer. Additionally, 3D culture revealed ependymal rosette formation and cilia-related ontologies, similar to in situ tumors. Our data confirm the validity of the 811 and 928 cell lines as representative models of intracranial, posterior fossa 1q+?EPN, which holds potential to advance translational science for patients affected by this tumor.
| S-EPMC5868094 | biostudies-literature
Project description:Our study demonstrated that the expression of Igf2bp1 in activated microglia was significantly up-regulated, implying a role of Igf2bp1 in LPS-induced m6A modifications in microglia. To understand the roles of Igf2bp1 on LPS-induced m6A modification in microglia, we performed Igf2bp1 loss-of-function (LOF) approach. Microglia stimulated by LPS were transfected with either scrambled siRNA control or Igf2bp1 siRNA for 48 hours. To m6A modification profiles in control and Igf2bp1 LOF microglia were determined by MeRIP-seq analysis.
2022-12-31 | E-MTAB-11411 | biostudies-arrayexpress