Project description:The aim of the project was to detect genomic regions that were normal, duplicated or deleted in these cell lines for transcription factors NFKBp50, NFkBp65, HIF1a and FAS gene which we studied. It is not clear the effects of copy number variations on allele specific assembly or disruption of master regulator transcription factors. Thus, the CNV analysis verified that 16HBE cell line, though transformed with defective simian virus, had normal copy number variations thus was a suitable source for nuclear extract to study the afore mentioned TFs. T84 showed duplications and large genomic deletions for TFs: NFkBp50 and p65. 16HBE and T84 are both epithelial cell lines type from human. 16HBE is derived from bronchial epithelium, while the T84 is derived from the colon carcinoma.
Project description:aCGH was performed on acute myeloid leukemia samples (vs constitutive Normal matched tissue) derived from a mouse model of mutant NPM1, NRAS and FLIT3 normal karyotype leukemia. The purpose of these assays was to identify common and potentially co-operative genetic phenomena in NPM1c positive mouse leukemias.
Project description:Recurrences of diffuse large B-cell lymphomas (DLBCL) result in significant morbidity and mortality, but their underlying genetic and biological mechanisms are unclear. Clonal relationship in DLBCL relapses so far is mostly addressed by the investigation of immunoglobulin (IG) rearrangements, therefore lacking deeper insights into genome-wide lymphoma evolution. We studied mutations and copy number aberrations in 20 paired relapsing and 20 non-relapsing DLBCL cases aiming to test the clonal relationship between primaries and relapses, to track tumorsâ genetic evolution and to investigate the genetic background of DLBCL recurrence. Three clonally-unrelated DLBCL relapses were identified (15%). Also, two distinct patterns of genetic evolution in clonally-related relapses were detected: (1) early-divergent/branching evolution from a common progenitor in 6 patients (30%), and (2) late-divergent/linear progression of relapses in 11 patients (65%). Analysis of recurrent genetic events identified potential early drivers of lymphomagenesis (KMT2D, MYD88, CD79B and PIM1). The most frequent relapse-specific events were additional mutations in KMT2D and alterations of MEF2B. SOCS1 mutations were exclusive to non-relapsing DLBCL, whereas primaries of relapsing DLBCL more commonly displayed gains of 10p15.3-p12.1 containing the potential oncogenes PRKCQ, GATA3, MLLT10 and ABI1. Altogether, our study expands knowledge on clonal relationship, genetic evolution and mutational basis of DLBCL relapses. There are 62 copy number Agilent 180k SurePrint arrays in total, which represent 40 cases. There are 21 arrays of primary relapsing DLBCL tumors, 21 arrys of matched relapses and 20 arrays of non relapsing DLBCLs.
Project description:Glioblastoma multiforme (GBM), the most common and malignant type of glioma, is characterized by a poor prognosis and the lack of an effective treatment, which are due to a small sub-population of cells with stem-like properties, termed glioma stem cells (GSCs). The term M-bM-^@M-^\multiformeM-bM-^@M-^] describes the histological feature of this tumor, i.e. the cellular and morphological heterogeneity. At the molecular level multiple layers of alterations may reflect this heterogeneity providing together the driving force of tumor initiation and development. In order to decipher the common M-bM-^@M-^\signatureM-bM-^@M-^] of the ancestral GSC population, we examined 5 already characterized GSC lines evaluating their copy number alterations using a genome-wide approach. Genomic DNA was isolated from 5 Glioma Stem Cell (GSC) lines. Each sample was labeled with Cy3 dye and then hybridized against the same commercial reference DNA labeled in Cy5.
Project description:Protein S-nitrosation (SNO-protein) is a post-translational modification in which a cysteine (Cys) residue is modified by nitric oxide (SNO-Cys). SNO-proteins impact many biological systems, but their identification has been technically challenging. We developed a chemical proteomic strategy - SNOTRAP (SNO trapping by triaryl phosphine) -that allows improved identification of SNO-proteins by mass spectrometry. We found that S-nitrosation is elevated during early stages of neurodegeneration, preceding cognitive decline. We identified changes in the SNOproteome during early neurodegeneration that are potentially relevant for synapse function, metabolism, and Alzheimer’s disease pathology. SNO-proteome analysis further reveals a potential linear motif for SNO-Cys sites that are altered during neurodegeneration. Our strategy can be applied to multiple cellular and disease contexts and can reveal signaling networks that aid drug development.
Project description:Acute myeloid leukemia with complex karyotype (CK-AML) is characterized by three or more chromosomal aberrations, and comprises 10–12% of AML patients. It is associated with complex chromosomal rearrangements, intra-tumor heterogeneity, therapy resistance and poor overall survival. We aimed to transcriptionally characterize CK-AML by performing RNA sequencing on blasts from 4 CK-AML patient samples.