ArrayCGH profiling of two B-cell lineage subpopulations in multiple myeloma
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ABSTRACT: ArrayCGH profiling and examination of IgH disruption by FISH on two myeloma B-cell lineage subpopulations: CD138+ and CD19+ to confirm existence of abnormal bone marrow B-cell subset contaning genetic background for primary oncogenic events.
Project description:In this paper, we demonstrated the possibility of effective utilization of oligonucleotide-based aCGH as a robust clinical tool for genome-wide scanning and detailed analysis of unbalanced genetic aberrations in 91 MM patients in combination with fluorescence in situ hybridization (FISH) in detection of high risk chromosomal aberrations. Loss of TP53 gene, translocation t(4;14)(p16;q32), gain in 1q21 and non-hyperdiploidy (non-hyperdiploid) area are associated with adverse prognosis in MM, thus their evaluation with other lesions obtained via genomic profiling could lead to better classification and risk assesment for thr patients.
Project description:Cytogenetic abnormalities (CA) are important clinical parameters in various types of cancer, including multiple myeloma (MM). We developed a model to predict CA in patients with MM using gene expression profiling (GEP) and validated it by different cytogenetic techniques. The model was shown to have an accuracy up to 0.89. These results provide proof of concept for the hypothesis that GEP could serve as a one-stop data source for clinical molecular diagnosis and/or prognosis. 92 paired RNA-DNA samples were hybridized to Affy U133Plus2 and Agilent 244K aCGH arrays and used as training set. Another 23 paired samples as test set.
Project description:This experiment follows, extends and validates our previous findings published in Leukemia & Lymphoma as original article entitled \Molecular heterogeneity and centrosome-associated genes in multiple myeloma\. [Kryukov F, Nemec P, et al, Leuk Lymphoma. 2013 Sep;54(9):1982-8. Doi: 10.3109/10428194.2013.764416] (ArrayExpress Accession E-MTAB-1038). This experiment submission is enriched by supplemental R-script-based data file named \for_external_validation.RData\ which includes script for CAGP model application.
Project description:Multiple myeloma (MM) is a malignant plasma cell tumor characterized by various chromosomal aberrations. From the aspect of epigenetics, hypomethylation of DNA repetitive elements has been considered to induce chromosomal instability. We therefore have been interested in how it is related to chromosomal aberrations in MM. To address this, methylation levels of repetitive elements (including LINE-1, Alu and Satellite-alpha) and copy number alterations were measured in clinical samples (N=85). Bisulfite-pyrosequencing (N=85) and array-based comparative genomic hybridization (N=73) were used for these measurement, respectively. As results, methylation levels of repetitive elements were linearly associated with the degree of malignancy of plasma cells. Combined with hierarchical clustering of the result of aCGH, hypomethylation of repetitive elements was well associated with frequent chromosomal deletions. In particular, methylation levels of LINE-1 was significantly higher in samples with chromosome 13 deletion than the other (36.1% vs. 44.0%, P=0.010). The number of deleted probes was significantly correlated with LINE-1 methylation levels (R=-0.531). Finally, we observed significantly poorer prognosis in the lower LINE-1 methylation group (HR=2.8, P=0.015, compared to the higher methylation group). In conclusion, DNA methylation levels of repetitive elements, especially of LINE-1, are associated with the frequency of chromosomal deletions and prognosis in MM. 67 MM samples and 6 monoclonal gammopathy of undetermined significance (MGUS) samples were analyzed, all samples were selected by CD138 sorting
Project description:The concept of the CpG island methylator phenotype (CIMP) in colorectal cancers (CRCs) is widely accepted, though the timing of its occurrence and its interaction with other genetic defects early during carcinogenesis remains largely unknown. Our aim was to uncover the molecular evolution of CIMP CRCs through integrative analysis of endoscopic, histological and molecular signatures in precancerous and malignant colorectal lesions. A total of 84 endoscopically obtained human colorectal tumor was analyzed using Agilent CGH microarray. Copy number aberration was compared with clinicopathological features and DNA methylation status.
Project description:Gastrointestinal stromal tumors (GISTs) are the most important mesenchymal tumors of the gastrointestinal tract. The vast majority of GISTs exhibit activating mutations of KIT or PDGFRA, but epigenetic alteration of GISTs is largely unknown. In this study, we aimed to clarify the involvement of DNA methylation in GIST malignancy. A total of 25 GIST specimens were studied using Human Genome CGH Microarray Kit 105A (G4412A, Agilent). Levels of LINE-1 methylation were analyzed using bisulfite-pyrosequencing. LINE-1 hypomethylation was correlated with risk grade, and high-risk GISTs exhibited lower levels of LINE-1 methylation than low- or intermediate-risk GISTs. Array CGH analysis revealed a significant correlation between LINE-1 hypomethylation and chromosomal aberrations. Our data suggest that LINE-1 hypomethylation correlates with the aggressiveness of GISTs. Hypomethylation may increase the malignant potential of GISTs by inducing accumulation of chromosomal aberrations. A total of 25 surgically obtained human gastrointestinal stromal tumors (GISTs) was analyzed using Agilent CGH microarray. Copy number aberration was compared with clinicopathological features and DNA methylation status.
Project description:The concept of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) is widely accepted, though the timing of its occurrence and its interaction with other genetic defects are not fully understood. Our aim in this study was to unravel the molecular development of CIMP cancers by dissecting their genetic and epigenetic signatures in precancerous and malignant colorectal lesions. A total of 88 samples (16 normal colon tissues taken from adjacent tumor tissue, 70 colorectal tumor tissues and 2 cell lines) was analyzed using MCA microarray. Aberrant DNA methylation was compared with clinicopathological features and copy number.
Project description:This SuperSeries is composed of the following subset Series: GSE35476: Array CGH analysis of human colorectal tumors GSE35508: Methylated CpG island amplification (MCA) microarray analysis of human colorectal tumors Refer to individual Series
Project description:Aberrant DNA methylation is implicated in the epigenetic field defect seen in gastric cancer (GC). Our aim in this study was to identify predictive biomarkers by screening for DNA methylation in noncancerous background gastric mucosa from GC patients. A total of 46 endoscopically obtained human gastric mucosa, 10 gastric cancer and 5 cell lines were analyzed using MCA microarray. Aberrant DNA methylation was compared with clinicopathological features. Healthy individuals were divided into two groups based on the types of chronic gastritis; A: antrum-predominant gastritis P or C: pangastritis or corpus-predominant gastritis
Project description:Enhancers are powerful regulatory regions, important for development and the maintenance of differentiated cells and tissues. Here, we generate global maps for two enhancer-associated histone marks, H3K4me1 and H3K27ac for a number of major human blood cell types. This data was generated to show that capped RNAs transcribed bidirectionally can identify known and novel enhancers in vivo. ChIP-seq of 2 histone marks in human blood monocytes, CD19+ B cells, CD8+ T cells, CD4+CD25-CD45RA+ naive T cells, & NK cells