25
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

      research-article
      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 references39

          • 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

            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
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Patterns of somatic structural variation in human cancer genomes

              A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes 1–7 . Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types 8 . Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions—as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2–7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and—in liver cancer—frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.
                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
                : 3361
                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
                Author information
                http://orcid.org/0000-0003-2567-0273
                http://orcid.org/0000-0003-4417-657X
                http://orcid.org/0000-0001-5773-7730
                http://orcid.org/0000-0001-9239-1050
                http://orcid.org/0000-0003-0646-0705
                http://orcid.org/0000-0002-0167-3771
                http://orcid.org/0000-0003-1702-348X
                http://orcid.org/0000-0001-9479-3010
                http://orcid.org/0000-0003-4476-6481
                http://orcid.org/0000-0002-6393-595X
                Article
                23695
                10.1038/s41467-021-23695-8
                8184748
                34099699
                1a436539-420c-46bb-8f48-0760f5da0d96
                © 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/.

                History
                : 4 December 2020
                : 10 May 2021
                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
                Uncategorized
                personalized medicine, lymphoma, cancer genomics, biomedical engineering

                Comments

                Comment on this article