3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing

      1 , 1 , 2 , 3 , 2 , 4 , 4 , 5 , 6 , 7 , 7 , 8 , 8 , 3 , 3 , 1 , 1 , 1 , 1 , 1 , 2 , 2 , 2 , 2 , 3 , 3 , 2 , , 2 , , 1

      Nature Communications

      Nature Publishing Group UK

      Personalized medicine, Lymphoma, Cancer genomics, Biomedical engineering

      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

          In routine diagnostic pathology, cancer biopsies are preserved by formalin-fixed, paraffin-embedding (FFPE) procedures for examination of (intra-) cellular morphology. Such procedures inadvertently induce DNA fragmentation, which compromises sequencing-based analyses of chromosomal rearrangements. Yet, rearrangements drive many types of hematolymphoid malignancies and solid tumors, and their manifestation is instructive for diagnosis, prognosis, and treatment. Here, we present FFPE-targeted locus capture (FFPE-TLC) for targeted sequencing of proximity-ligation products formed in FFPE tissue blocks, and PLIER, a computational framework that allows automated identification and characterization of rearrangements involving selected, clinically relevant, loci. FFPE-TLC, blindly applied to 149 lymphoma and control FFPE samples, identifies the known and previously uncharacterized rearrangement partners. It outperforms fluorescence in situ hybridization (FISH) in sensitivity and specificity, and shows clear advantages over standard capture-NGS methods, finding rearrangements involving repetitive sequences which they typically miss. FFPE-TLC is therefore a powerful clinical diagnostics tool for accurate targeted rearrangement detection in FFPE specimens.

          Abstract

          Preservation of cancer biopsies by FFPE introduces DNA fragmentation, hindering analysis of rearrangements. Here the authors introduce FFPE Targeted Locus Capture for identification of translocations in preserved samples.

          Related collections

          Most cited references 39

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

          Circos: an information aesthetic for comparative genomics.

          We created a visualization tool called Circos to facilitate the identification and analysis of similarities and differences arising from comparisons of genomes. Our tool is effective in displaying variation in genome structure and, generally, any other kind of positional relationships between genomic intervals. Such data are routinely produced by sequence alignments, hybridization arrays, genome mapping, and genotyping studies. Circos uses a circular ideogram layout to facilitate the display of relationships between pairs of positions by the use of ribbons, which encode the position, size, and orientation of related genomic elements. Circos is capable of displaying data as scatter, line, and histogram plots, heat maps, tiles, connectors, and text. Bitmap or vector images can be created from GFF-style data inputs and hierarchical configuration files, which can be easily generated by automated tools, making Circos suitable for rapid deployment in data analysis and reporting pipelines.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Robust 4C-seq data analysis to screen for regulatory DNA interactions.

            Regulatory DNA elements can control the expression of distant genes via physical interactions. Here we present a cost-effective methodology and computational analysis pipeline for robust characterization of the physical organization around selected promoters and other functional elements using chromosome conformation capture combined with high-throughput sequencing (4C-seq). Our approach can be multiplexed and routinely integrated with other functional genomics assays to facilitate physical characterization of gene regulation.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Capturing chromosome conformation.

              We describe an approach to detect the frequency of interaction between any two genomic loci. Generation of a matrix of interaction frequencies between sites on the same or different chromosomes reveals their relative spatial disposition and provides information about the physical properties of the chromatin fiber. This methodology can be applied to the spatial organization of entire genomes in organisms from bacteria to human. Using the yeast Saccharomyces cerevisiae, we could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis. We also analyzed yeast chromosome III at the G1 stage of the cell cycle. We found that chromatin is highly flexible throughout. Furthermore, functionally distinct AT- and GC-rich domains were found to exhibit different conformations, and a population-average 3D model of chromosome III could be determined. Chromosome III emerges as a contorted ring.
                Bookmark

                Author and article information

                Contributors
                erik.splinter@cergentis.com
                w.laat@hubrecht.eu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                7 June 2021
                7 June 2021
                2021
                : 12
                Affiliations
                [1 ]GRID grid.7692.a, ISNI 0000000090126352, Oncode Institute & Hubrecht Institute-KNAW and University Medical Center Utrecht, ; Utrecht, the Netherlands
                [2 ]Cergentis BV, Utrecht, the Netherlands
                [3 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Amsterdam UMC-Vrije Universiteit Amsterdam, Department of Pathology and Cancer Center Amsterdam, ; Amsterdam, the Netherlands
                [4 ]GRID grid.7692.a, ISNI 0000000090126352, University Medical Centre Utrecht, Department of Pathology, ; Utrecht, the Netherlands
                [5 ]Laboratorium Pathologie Oost-Nederland, Hengelo, the Netherlands
                [6 ]GRID grid.10419.3d, ISNI 0000000089452978, Leiden University Medical Centre, Department of Hematology, ; Leiden, the Netherlands
                [7 ]GRID grid.10419.3d, ISNI 0000000089452978, Leiden University Medical Center, Department of Pathology, ; Leiden, the Netherlands
                [8 ]GRID grid.4494.d, ISNI 0000 0000 9558 4598, University of Groningen, University Medical Centre Groningen, Department of Pathology & Medical Biology, ; Groningen, the Netherlands
                Article
                23695
                10.1038/s41467-021-23695-8
                8184748
                34099699
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                Funding
                Funded by: FundRef https://doi.org/10.13039/501100004622, KWF Kankerbestrijding (Dutch Cancer Society);
                Award ID: 11632/2018-1
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized

                personalized medicine, lymphoma, cancer genomics, biomedical engineering

                Comments

                Comment on this article