Project description:Amplification or gain of chromosome 1q (+1q) is a common genomic alteration occurring in nearly 40% of multiple myeloma patients. Although it is associated with poor prognosis and advanced disease stages, the impact of +1q at the proteomic level remains unclear. Here, we studied sorted CD138+ plasma cells from the bone marrow from newly diagnosed multiple myeloma to uncover molecular alterations associated with +1q. Differential expression analysis revealed significantly increased expression of several proteins encoded by 1q region indicating potential gene dosage effect. Protein pathway enrichment analysis identified enrichment of cell cycle pathway among proteins with increased expression in +1q. Further, protein-protein interaction network analysis showed enrichment of MYC transcriptional targets including increased expression of TIPRL (located on 1q23) in +1q cases. In agreement with these findings, increased TIPRL transcript expression was correlated with +1q across different primary driver genomic alterations in MM in the CoMMPass dataset. High TIPRL protein expression was further associated with poor prognosis in cases with hyperdiploidy. Overall, this study highlights the role of proteomics in understanding molecular events associated with chromosomal alterations in multiple myeloma and identifying potential targets for further functional analysis.
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.
Project description:Comparison of expression profiles in early Drosophila embryos and unfertilised eggs (collection intervals: 30-60 min, 90-120 min and 150-180 min after egg laying). A complete summary file containing normalized data with FLYBASE CG gene identifiers, gene symbols and classifications can be found in E-MEXP-2580.additional.zip under the "Browse all available files" link
Project description:Amplification or gain of chromosome 1q (+1q) is a common genomic alteration occurring in the plasma cells in nearly 40% of multiple myeloma patients. Although it is associated with inferior outcomes and is more common in the relapsed or refractory advanced disease stages, the impact of +1q at the proteomic level remains unclear. Here, we studied enriched CD138+ bone marrow plasma cells in newly diagnosed multiple myeloma to uncover molecular alterations associated with +1q. Differential expression analysis revealed significantly increased expression of several proteins encoded by 1q region indicating potential gene dosage effect. Pathway enrichment analysis identified enrichment of cell cycle proteins. Further, protein-protein interaction network analysis showed enrichment of MYC transcriptional targets in +1q cases, including increased expression of TIPRL (located on 1q23). In agreement with these findings, increased TIPRL transcript expression was correlated with +1q across different cytogenetic subgroups in the CoMMPass dataset. High TIPRL protein expression was associated with poor prognosis in patients from the hyperdiploidy subgroup. Overall, this study highlights the role of proteomics in understanding molecular events associated with chromosomal alterations in MM and identifying potential targets for further functional analysis.
Project description:Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaic copy number gain of chromosome 1q is associated with cortical malformations, early-onset epilepsy, and developmental delay. Pathogenic brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in a neural progenitor cell during fetal development. However, in our cohort, in at least five of six patients with brain mosaic copy number gain of chromosome 1q, the alteration occurred pre-conception. We observed a third non-constitutive, but parentally-derived, haplotype for chromosome 1q in patient brain tissue, demonstrating that the copy number alteration occurred in a gamete pre-conception. The altered cells had no representation in parental buccal or proband blood or buccal samples, but were prominently observed in proband brain tissue, suggesting the copy number gain was lost in most cell lineages during embryonic development. Single-nuclei genotyping coupled with gene expression profiling revealed a strong enrichment of the chromosome 1q gain in astrocytes, which correlated with the unusual finding of hyaline astrocytic inclusions in all six cases.
Project description:Jumping translocations are cytogenetic abnormalities associated with poor clinical outcome and progression in Myelodysplastic Syndromes/Acute Myeloid Leukemia (MDS/AML).Typically a donor chromosome, often a trisomic 1q, is transferred onto 2 or more recipient chromosomes. Previous studies have demonstrated the crosstalk between DNA hypomethylation and 1q trisomy. Here, we used an epi-genomic approach in sequential samples from a cohort of MDS and AML with the appearance of 1q jumping translocations after 5’-azacytidine (AZA) treatment.
Project description:Genomewide mapping of D. melanogaster Biniou protein binding during embryonic development. Three consecutive timepoints (6-8, 8-10, 10-12 hrs after egg-laying) were assayed in two independent repeats each. Two different antibodies were used to precipitate the Biniou protein. Additionally the respective preimmune-serum was used as a control for every precipitation. The enriched DNA was hybridized to high density Affymetrix GeneChip Drosophila Tiling 1.0R array.