41
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Identifying putative breast cancer-associated long intergenic non-coding RNA loci by high density SNP array analysis

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Recent high-throughput transcript discoveries have yielded a growing recognition of long intergenic non-coding RNAs (lincRNAs), a class of arbitrarily defined transcripts (>200 nt) that are primarily produced from the intergenic space. lincRNAs have been increasingly acknowledged for their expressional dynamics and likely functional associations with cancers. However, differential gene dosage of lincRNA genes between cancer genomes is less studied. By using the high-density Human Omni5-Quad BeadChips (Illumina), we investigated genomic copy number aberrations in a set of seven tumor-normal paired primary human mammary epithelial cells (HMECs) established from patients with invasive ductal carcinoma. This Beadchip platform includes a total of 2,435,915 SNP loci dispersed at an average interval of ~700 nt throughout the intergenic region of the human genome. We mapped annotated or putative lincRNA genes to a subset of 332,539 SNP loci, which were included in our analysis for lincRNA-associated copy number variations (CNV). We have identified 122 lincRNAs, which were affected by somatic CNV with overlapped aberrations ranging from 0.14% to 100% in length. lincRNA-associated aberrations were detected predominantly with copy number losses and preferential clustering to the ends of chromosomes. Interestingly, lincRNA genes appear to be less susceptible to CNV in comparison to both protein-coding and intergenic regions (CNV affected segments in percentage: 1.8%, 37.5%, and 60.6%, respectively). In summary, our study established a novel approach utilizing high-resolution SNP array to identify lincRNA candidates, which could functionally link to tumorigenesis, and provide new strategies for the diagnosis and treatment of breast cancer.

          Related collections

          Most cited references18

          • Record: found
          • Abstract: found
          • Article: not found

          The transcriptional landscape of the mammalian genome.

          This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Structural variation in the human genome.

            The first wave of information from the analysis of the human genome revealed SNPs to be the main source of genetic and phenotypic human variation. However, the advent of genome-scanning technologies has now uncovered an unexpectedly large extent of what we term 'structural variation' in the human genome. This comprises microscopic and, more commonly, submicroscopic variants, which include deletions, duplications and large-scale copy-number variants - collectively termed copy-number variants or copy-number polymorphisms - as well as insertions, inversions and translocations. Rapidly accumulating evidence indicates that structural variants can comprise millions of nucleotides of heterogeneity within every genome, and are likely to make an important contribution to human diversity and disease susceptibility.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.

              There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise. Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified approximately 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFkappaB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.
                Bookmark

                Author and article information

                Journal
                Front Genet
                Front Genet
                Front. Gene.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                21 December 2012
                2012
                : 3
                : 299
                Affiliations
                [1] 1Cancer Biology Program, Fox Chase Cancer Center Philadelphia, PA, USA
                [2] 2Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center Philadelphia, PA, USA
                [3] 3Department of Clinical Genetics, Fox Chase Cancer Center Philadelphia, PA, USA
                Author notes

                Edited by: Peng Jin, Emory University School of Medicine, USA

                Reviewed by: Fatah Kashanchi, George Mason University, USA; Amelia Cimmino, Consiglio Nazionale delle Ricerche, Italy

                *Correspondence: Xiaowei Chen, Cancer Biology Program, Fox Chase Cancer Center, w363, 333 Cottman Avenue, Philadelphia, PA 19111, USA. e-mail: xiaowei.chen@ 123456fccc.edu

                This article was submitted to Frontiers in Non-Coding RNA, a specialty of Frontiers in Genetics.

                Article
                10.3389/fgene.2012.00299
                3528021
                23267367
                da3589fb-1c84-4587-87a2-58aa364f0f58
                Copyright © 2012 Jiang, Zhou, Devarajan, Slater, Daly and Chen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 31 August 2012
                : 04 December 2012
                Page count
                Figures: 3, Tables: 6, Equations: 0, References: 31, Pages: 9, Words: 5640
                Categories
                Genetics
                Original Research Article

                Genetics
                long intergenic non-coding rna (lincrna),copy number variation (cnv),snp array,breast cancer

                Comments

                Comment on this article