Project description:This series represents the data set of Array CGH from the paper (submit for publication): “Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas. Mestre et all. ” and it's web supplement. The molecular nature of many secondary events in the pathogenesis of B-cell non Hodgkin lymphoma (B-NHL) remains unknown. We used high-resolution CGH to BAC microarrays to characterize the genomes of 48 B-cell non-Hodgkin lymphoma (B-NHL) cell lines of different origins. Array CGH identified, on average, 20 genomic alterations per cell line, including regional gains and losses as well as previously uncharacterized aberrations. Different genomic patterns were observed among the B-NHL subtypes. To search for possible oncogenic target genes, gene expression profiling was performed in the cell lines models. Integrative genomic and gene expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated twenty homozygous deletions at seven chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them were frequently silenced by epigenetic mechanisms. Our microarray strategy has identified novel candidate suppressors inactivated by genetic and epigenetic mechanisms that substantially vary among the B-NHL subtypes. Keywords: Array CGH, B-cell non-Hodgkin lymphoma, genomic amplification, homozygous deletion
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes