Dual-molecular barcode sequencing detects rare variants in tumor and cell free DNA in plasma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-02-25

AUTHORS

Yosuke Hirotsu, Sotaro Otake, Hiroshi Ohyama, Kenji Amemiya, Rumi Higuchi, Toshio Oyama, Hitoshi Mochizuki, Taichiro Goto, Masao Omata

ABSTRACT

Conventional next generation sequencing analysis has provided important insights into cancer genetics. However, the detection of rare (low allele fraction) variants remains difficult because of the error-prone nucleotide changes derived from sequencing/PCR errors. To eliminate the false-positive variants and detect genuine rare variants, sequencing technology combined with molecular barcodes will be useful. Here, we used the newly developed dual-molecular barcode technology (Ion AmpliSeq HD) to analyze somatic mutations in 24 samples (12 tumor tissues and 12 plasma) from 12 patients with biliary-pancreatic and non-small cell lung cancers. We compared the results between next generation sequencing analysis with or without molecular barcode technologies. The variant allele fraction (VAF) between non-molecular barcode and molecular barcode sequencing was correlated in plasma DNA (R2 = 0.956) and tumor (R2 = 0.935). Both methods successfully detected high VAF mutations, however, rare variants were only identified by molecular barcode sequencing and not by non-molecular barcode sequencing. Some of these rare variants in tumors were annotated as pathogenic, and therefore subclonal driver mutations could be observed. Furthermore, the very low VAF down to 0.17% were identified in cell free DNA in plasma. These results demonstrate that the dual molecular barcode sequencing technologies can sensitively detect rare somatic mutations, and will be important in the investigation of the clonal and subclonal architectures of tumor heterogeneity. More... »

PAGES

3391

References to SciGraph publications

  • 2013-11-03. Activating ESR1 mutations in hormone-resistant metastatic breast cancer in NATURE GENETICS
  • 2017-02-24. Liquid biopsies come of age: towards implementation of circulating tumour DNA in NATURE REVIEWS CANCER
  • 2013-11-03. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas in NATURE GENETICS
  • 2015-08-10. Genomic spectra of biliary tract cancer in NATURE GENETICS
  • 2017-02-15. Whole-genome landscape of pancreatic neuroendocrine tumours in NATURE
  • 2016-12-08. Acquired RAS or EGFR mutations and duration of response to EGFR blockade in colorectal cancer in NATURE COMMUNICATIONS
  • 2012-06-13. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer in NATURE
  • 2016-10-26. Comparison between two amplicon-based sequencing panels of different scales in the detection of somatic mutations associated with gastric cancer in BMC GENOMICS
  • 2016-03-28. Integrated digital error suppression for improved detection of circulating tumor DNA in NATURE BIOTECHNOLOGY
  • 2019-01-21. Molecular subtype switching in early-stage gastric cancers with multiple occurrences in JOURNAL OF GASTROENTEROLOGY
  • 2016-11-29. Intrinsic HER2 V777L mutation mediates resistance to trastuzumab in a breast cancer patient in MEDICAL ONCOLOGY
  • 2016-02-24. Genomic analyses identify molecular subtypes of pancreatic cancer in NATURE
  • 2015-05-04. Acquired EGFR C797S mediates resistance to AZD9291 in advanced non-small cell lung cancer harboring EGFR T790M in NATURE MEDICINE
  • 2016-02-20. Analysis of tumor-derived DNA in plasma and bone marrow fluid in lung cancer patients in MEDICAL ONCOLOGY
  • 2009-12. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M in NATURE
  • 2018-03-26. Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations in NATURE REVIEWS GENETICS
  • 2017-01-19. Stepwise addition of genetic changes correlated with histological change from “well-differentiated” to “sarcomatoid” phenotypes: a case report in BMC CANCER
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-020-60361-3

    DOI

    http://dx.doi.org/10.1038/s41598-020-60361-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1125099321

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32099048


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Genetics", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Alleles", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Carcinoma, Non-Small-Cell Lung", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell-Free Nucleic Acids", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "DNA Barcoding, Taxonomic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "High-Throughput Nucleotide Sequencing", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Lung Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Pancreatic Neoplasms", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Genome Analysis Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Genome Analysis Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hirotsu", 
            "givenName": "Yosuke", 
            "id": "sg:person.01104463136.69", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01104463136.69"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Lung Cancer and Respiratory Disease Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Lung Cancer and Respiratory Disease Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Otake", 
            "givenName": "Sotaro", 
            "id": "sg:person.0705402562.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0705402562.34"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Gastroenterology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan", 
              "id": "http://www.grid.ac/institutes/grid.136304.3", 
              "name": [
                "Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan", 
                "Department of Gastroenterology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ohyama", 
            "givenName": "Hiroshi", 
            "id": "sg:person.01176700500.71", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01176700500.71"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Genome Analysis Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Genome Analysis Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Amemiya", 
            "givenName": "Kenji", 
            "id": "sg:person.01271466715.07", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01271466715.07"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Lung Cancer and Respiratory Disease Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Lung Cancer and Respiratory Disease Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Higuchi", 
            "givenName": "Rumi", 
            "id": "sg:person.016365545233.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016365545233.50"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pathology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Department of Pathology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Oyama", 
            "givenName": "Toshio", 
            "id": "sg:person.011405362052.18", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011405362052.18"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan", 
              "id": "http://www.grid.ac/institutes/grid.417333.1", 
              "name": [
                "Genome Analysis Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan", 
                "Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mochizuki", 
            "givenName": "Hitoshi", 
            "id": "sg:person.01335140136.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01335140136.50"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Lung Cancer and Respiratory Disease Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Lung Cancer and Respiratory Disease Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Goto", 
            "givenName": "Taichiro", 
            "id": "sg:person.0605677542.20", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605677542.20"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan", 
              "id": "http://www.grid.ac/institutes/grid.26999.3d", 
              "name": [
                "Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan", 
                "The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Omata", 
            "givenName": "Masao", 
            "id": "sg:person.0775700471.08", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0775700471.08"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/nature11156", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024120060", 
              "https://doi.org/10.1038/nature11156"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrg.2017.117", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101760979", 
              "https://doi.org/10.1038/nrg.2017.117"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12885-017-3059-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053913316", 
              "https://doi.org/10.1186/s12885-017-3059-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s12032-016-0857-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005513585", 
              "https://doi.org/10.1007/s12032-016-0857-2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms13665", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017620814", 
              "https://doi.org/10.1038/ncomms13665"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature16965", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031075239", 
              "https://doi.org/10.1038/nature16965"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature08622", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009588480", 
              "https://doi.org/10.1038/nature08622"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12864-016-3166-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039726049", 
              "https://doi.org/10.1186/s12864-016-3166-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2813", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049645772", 
              "https://doi.org/10.1038/ng.2813"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm.3854", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005299046", 
              "https://doi.org/10.1038/nm.3854"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2823", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010741940", 
              "https://doi.org/10.1038/ng.2823"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.3375", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040279504", 
              "https://doi.org/10.1038/ng.3375"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.3520", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042966935", 
              "https://doi.org/10.1038/nbt.3520"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc.2017.7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1083863116", 
              "https://doi.org/10.1038/nrc.2017.7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s12032-016-0744-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051585301", 
              "https://doi.org/10.1007/s12032-016-0744-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00535-019-01547-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1111577150", 
              "https://doi.org/10.1007/s00535-019-01547-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature21063", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1083822538", 
              "https://doi.org/10.1038/nature21063"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2020-02-25", 
        "datePublishedReg": "2020-02-25", 
        "description": "Conventional next generation sequencing analysis has provided important insights into cancer genetics. However, the detection of rare (low allele fraction) variants remains difficult because of the error-prone nucleotide changes derived from sequencing/PCR errors. To eliminate the false-positive variants and detect genuine rare variants, sequencing technology combined with molecular barcodes will be useful. Here, we used the newly developed dual-molecular barcode technology (Ion AmpliSeq HD) to analyze somatic mutations in 24 samples (12 tumor tissues and 12 plasma) from 12 patients with biliary-pancreatic and non-small cell lung cancers. We compared the results between next generation sequencing analysis with or without molecular barcode technologies. The variant allele fraction (VAF) between non-molecular barcode and molecular barcode sequencing was correlated in plasma DNA (R2\u2009=\u20090.956) and tumor (R2\u2009=\u20090.935). Both methods successfully detected high VAF mutations, however, rare variants were only identified by molecular barcode sequencing and not by non-molecular barcode sequencing. Some of these rare variants in tumors were annotated as pathogenic, and therefore subclonal driver mutations could be observed. Furthermore, the very low VAF down to 0.17% were identified in cell free DNA in plasma. These results demonstrate that the dual molecular barcode sequencing technologies can sensitively detect rare somatic mutations, and will be important in the investigation of the clonal and subclonal architectures of tumor heterogeneity.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41598-020-60361-3", 
        "inLanguage": "en", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.7543122", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1045337", 
            "issn": [
              "2045-2322"
            ], 
            "name": "Scientific Reports", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "10"
          }
        ], 
        "keywords": [
          "molecular barcode sequencing", 
          "cell-free DNA", 
          "variant allele fraction", 
          "rare variants", 
          "non-small cell lung cancer", 
          "cell lung cancer", 
          "somatic mutations", 
          "low variant allele fractions", 
          "lung cancer", 
          "next-generation sequencing analysis", 
          "plasma DNA", 
          "tumors", 
          "driver mutations", 
          "tumor heterogeneity", 
          "rare somatic mutations", 
          "free DNA", 
          "generation sequencing analysis", 
          "allele fraction", 
          "subclonal architecture", 
          "cancer genetics", 
          "barcode sequencing", 
          "sequencing analysis", 
          "mutations", 
          "nucleotide changes", 
          "patients", 
          "subclonal driver mutations", 
          "cancer", 
          "variants", 
          "sequencing", 
          "plasma", 
          "sequencing technologies", 
          "molecular barcodes", 
          "DNA", 
          "false positive variants", 
          "barcodes", 
          "important insights", 
          "PCR errors", 
          "analysis", 
          "changes", 
          "heterogeneity", 
          "results", 
          "genetics", 
          "samples", 
          "barcode technology", 
          "detection", 
          "fraction", 
          "investigation", 
          "next generation", 
          "insights", 
          "method", 
          "generation", 
          "technology", 
          "architecture", 
          "error", 
          "Conventional next generation sequencing analysis", 
          "error-prone nucleotide changes", 
          "genuine rare variants", 
          "dual-molecular barcode technology", 
          "molecular barcode technologies", 
          "non-molecular barcode", 
          "high VAF mutations", 
          "VAF mutations", 
          "non-molecular barcode sequencing", 
          "dual molecular barcode sequencing technologies", 
          "molecular barcode sequencing technologies", 
          "barcode sequencing technologies", 
          "Dual-molecular barcode sequencing detects rare variants", 
          "barcode sequencing detects rare variants", 
          "sequencing detects rare variants", 
          "detects rare variants"
        ], 
        "name": "Dual-molecular barcode sequencing detects rare variants in tumor and cell free DNA in plasma", 
        "pagination": "3391", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1125099321"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41598-020-60361-3"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "32099048"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41598-020-60361-3", 
          "https://app.dimensions.ai/details/publication/pub.1125099321"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-01-01T18:57", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220101/entities/gbq_results/article/article_864.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41598-020-60361-3"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-020-60361-3'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-020-60361-3'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-020-60361-3'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-020-60361-3'


     

    This table displays all metadata directly associated to this object as RDF triples.

    309 TRIPLES      22 PREDICATES      122 URIs      97 LITERALS      16 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41598-020-60361-3 schema:about N03f2441ecff44d3491c314b6fa32876b
    2 N3455f926d10f464fa8b291e0d5aac691
    3 N3bd323b2ac8f46649f5b889fa328a613
    4 N5b0516ad73164b958a36be7b38668180
    5 N6c3b45e67c8d4367a1bbc8d2436de4f9
    6 N78aa310a92e84589bcf8942205667583
    7 N78c4d51f553b4cadb8950ed12683a482
    8 Ncc13c74b547e45f991a21abf585dd157
    9 Nced689f1b2714238b7f23e02123b5f23
    10 anzsrc-for:06
    11 anzsrc-for:0604
    12 schema:author Nf094f4fc30cb4ca1a4940bab6f366d69
    13 schema:citation sg:pub.10.1007/s00535-019-01547-z
    14 sg:pub.10.1007/s12032-016-0744-x
    15 sg:pub.10.1007/s12032-016-0857-2
    16 sg:pub.10.1038/nature08622
    17 sg:pub.10.1038/nature11156
    18 sg:pub.10.1038/nature16965
    19 sg:pub.10.1038/nature21063
    20 sg:pub.10.1038/nbt.3520
    21 sg:pub.10.1038/ncomms13665
    22 sg:pub.10.1038/ng.2813
    23 sg:pub.10.1038/ng.2823
    24 sg:pub.10.1038/ng.3375
    25 sg:pub.10.1038/nm.3854
    26 sg:pub.10.1038/nrc.2017.7
    27 sg:pub.10.1038/nrg.2017.117
    28 sg:pub.10.1186/s12864-016-3166-4
    29 sg:pub.10.1186/s12885-017-3059-1
    30 schema:datePublished 2020-02-25
    31 schema:datePublishedReg 2020-02-25
    32 schema:description Conventional next generation sequencing analysis has provided important insights into cancer genetics. However, the detection of rare (low allele fraction) variants remains difficult because of the error-prone nucleotide changes derived from sequencing/PCR errors. To eliminate the false-positive variants and detect genuine rare variants, sequencing technology combined with molecular barcodes will be useful. Here, we used the newly developed dual-molecular barcode technology (Ion AmpliSeq HD) to analyze somatic mutations in 24 samples (12 tumor tissues and 12 plasma) from 12 patients with biliary-pancreatic and non-small cell lung cancers. We compared the results between next generation sequencing analysis with or without molecular barcode technologies. The variant allele fraction (VAF) between non-molecular barcode and molecular barcode sequencing was correlated in plasma DNA (R<sup>2</sup> = 0.956) and tumor (R<sup>2</sup> = 0.935). Both methods successfully detected high VAF mutations, however, rare variants were only identified by molecular barcode sequencing and not by non-molecular barcode sequencing. Some of these rare variants in tumors were annotated as pathogenic, and therefore subclonal driver mutations could be observed. Furthermore, the very low VAF down to 0.17% were identified in cell free DNA in plasma. These results demonstrate that the dual molecular barcode sequencing technologies can sensitively detect rare somatic mutations, and will be important in the investigation of the clonal and subclonal architectures of tumor heterogeneity.
    33 schema:genre article
    34 schema:inLanguage en
    35 schema:isAccessibleForFree true
    36 schema:isPartOf N47e872556c30421a8546dca45ded122f
    37 N708309fa317a4e69a25f72e2362b812c
    38 sg:journal.1045337
    39 schema:keywords Conventional next generation sequencing analysis
    40 DNA
    41 Dual-molecular barcode sequencing detects rare variants
    42 PCR errors
    43 VAF mutations
    44 allele fraction
    45 analysis
    46 architecture
    47 barcode sequencing
    48 barcode sequencing detects rare variants
    49 barcode sequencing technologies
    50 barcode technology
    51 barcodes
    52 cancer
    53 cancer genetics
    54 cell lung cancer
    55 cell-free DNA
    56 changes
    57 detection
    58 detects rare variants
    59 driver mutations
    60 dual molecular barcode sequencing technologies
    61 dual-molecular barcode technology
    62 error
    63 error-prone nucleotide changes
    64 false positive variants
    65 fraction
    66 free DNA
    67 generation
    68 generation sequencing analysis
    69 genetics
    70 genuine rare variants
    71 heterogeneity
    72 high VAF mutations
    73 important insights
    74 insights
    75 investigation
    76 low variant allele fractions
    77 lung cancer
    78 method
    79 molecular barcode sequencing
    80 molecular barcode sequencing technologies
    81 molecular barcode technologies
    82 molecular barcodes
    83 mutations
    84 next generation
    85 next-generation sequencing analysis
    86 non-molecular barcode
    87 non-molecular barcode sequencing
    88 non-small cell lung cancer
    89 nucleotide changes
    90 patients
    91 plasma
    92 plasma DNA
    93 rare somatic mutations
    94 rare variants
    95 results
    96 samples
    97 sequencing
    98 sequencing analysis
    99 sequencing detects rare variants
    100 sequencing technologies
    101 somatic mutations
    102 subclonal architecture
    103 subclonal driver mutations
    104 technology
    105 tumor heterogeneity
    106 tumors
    107 variant allele fraction
    108 variants
    109 schema:name Dual-molecular barcode sequencing detects rare variants in tumor and cell free DNA in plasma
    110 schema:pagination 3391
    111 schema:productId N59acf69b75f547ae900f1942ab6b8778
    112 N651134100c764c689f6fec415b5d869f
    113 N9e4cf8e41b204b9e9502b740a26116e5
    114 schema:sameAs https://app.dimensions.ai/details/publication/pub.1125099321
    115 https://doi.org/10.1038/s41598-020-60361-3
    116 schema:sdDatePublished 2022-01-01T18:57
    117 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    118 schema:sdPublisher Nde4eab4aeadb4b6daa79bbfe670f786b
    119 schema:url https://doi.org/10.1038/s41598-020-60361-3
    120 sgo:license sg:explorer/license/
    121 sgo:sdDataset articles
    122 rdf:type schema:ScholarlyArticle
    123 N03f2441ecff44d3491c314b6fa32876b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    124 schema:name Carcinoma, Non-Small-Cell Lung
    125 rdf:type schema:DefinedTerm
    126 N0d7c54e281f44f08b08bca5dec98b91b rdf:first sg:person.01335140136.50
    127 rdf:rest N42f64314675c4d92a9add742481b106d
    128 N1518e4ba56374a839645fde760c654a1 rdf:first sg:person.01176700500.71
    129 rdf:rest N8cf05b3365fc49bbb139794f0c31dd0c
    130 N3455f926d10f464fa8b291e0d5aac691 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    131 schema:name Lung Neoplasms
    132 rdf:type schema:DefinedTerm
    133 N3bd323b2ac8f46649f5b889fa328a613 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    134 schema:name Humans
    135 rdf:type schema:DefinedTerm
    136 N42f64314675c4d92a9add742481b106d rdf:first sg:person.0605677542.20
    137 rdf:rest Nc03e4d50553546f3b9b569b531daa26e
    138 N47e872556c30421a8546dca45ded122f schema:issueNumber 1
    139 rdf:type schema:PublicationIssue
    140 N59acf69b75f547ae900f1942ab6b8778 schema:name pubmed_id
    141 schema:value 32099048
    142 rdf:type schema:PropertyValue
    143 N5b0516ad73164b958a36be7b38668180 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    144 schema:name Mutation
    145 rdf:type schema:DefinedTerm
    146 N5c84d4db01dd4abaa3b635c62a6281bc rdf:first sg:person.0705402562.34
    147 rdf:rest N1518e4ba56374a839645fde760c654a1
    148 N651134100c764c689f6fec415b5d869f schema:name doi
    149 schema:value 10.1038/s41598-020-60361-3
    150 rdf:type schema:PropertyValue
    151 N6c3b45e67c8d4367a1bbc8d2436de4f9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    152 schema:name Alleles
    153 rdf:type schema:DefinedTerm
    154 N6f148506f41748c4b038c899c10db5a9 rdf:first sg:person.011405362052.18
    155 rdf:rest N0d7c54e281f44f08b08bca5dec98b91b
    156 N708309fa317a4e69a25f72e2362b812c schema:volumeNumber 10
    157 rdf:type schema:PublicationVolume
    158 N78aa310a92e84589bcf8942205667583 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    159 schema:name Cell-Free Nucleic Acids
    160 rdf:type schema:DefinedTerm
    161 N78c4d51f553b4cadb8950ed12683a482 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    162 schema:name Pancreatic Neoplasms
    163 rdf:type schema:DefinedTerm
    164 N8cf05b3365fc49bbb139794f0c31dd0c rdf:first sg:person.01271466715.07
    165 rdf:rest Nd0e76b14ce4342ec9f2518367e5c660b
    166 N9e4cf8e41b204b9e9502b740a26116e5 schema:name dimensions_id
    167 schema:value pub.1125099321
    168 rdf:type schema:PropertyValue
    169 Nc03e4d50553546f3b9b569b531daa26e rdf:first sg:person.0775700471.08
    170 rdf:rest rdf:nil
    171 Ncc13c74b547e45f991a21abf585dd157 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    172 schema:name High-Throughput Nucleotide Sequencing
    173 rdf:type schema:DefinedTerm
    174 Nced689f1b2714238b7f23e02123b5f23 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    175 schema:name DNA Barcoding, Taxonomic
    176 rdf:type schema:DefinedTerm
    177 Nd0e76b14ce4342ec9f2518367e5c660b rdf:first sg:person.016365545233.50
    178 rdf:rest N6f148506f41748c4b038c899c10db5a9
    179 Nde4eab4aeadb4b6daa79bbfe670f786b schema:name Springer Nature - SN SciGraph project
    180 rdf:type schema:Organization
    181 Nf094f4fc30cb4ca1a4940bab6f366d69 rdf:first sg:person.01104463136.69
    182 rdf:rest N5c84d4db01dd4abaa3b635c62a6281bc
    183 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    184 schema:name Biological Sciences
    185 rdf:type schema:DefinedTerm
    186 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
    187 schema:name Genetics
    188 rdf:type schema:DefinedTerm
    189 sg:grant.7543122 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-020-60361-3
    190 rdf:type schema:MonetaryGrant
    191 sg:journal.1045337 schema:issn 2045-2322
    192 schema:name Scientific Reports
    193 schema:publisher Springer Nature
    194 rdf:type schema:Periodical
    195 sg:person.01104463136.69 schema:affiliation grid-institutes:None
    196 schema:familyName Hirotsu
    197 schema:givenName Yosuke
    198 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01104463136.69
    199 rdf:type schema:Person
    200 sg:person.011405362052.18 schema:affiliation grid-institutes:None
    201 schema:familyName Oyama
    202 schema:givenName Toshio
    203 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011405362052.18
    204 rdf:type schema:Person
    205 sg:person.01176700500.71 schema:affiliation grid-institutes:grid.136304.3
    206 schema:familyName Ohyama
    207 schema:givenName Hiroshi
    208 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01176700500.71
    209 rdf:type schema:Person
    210 sg:person.01271466715.07 schema:affiliation grid-institutes:None
    211 schema:familyName Amemiya
    212 schema:givenName Kenji
    213 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01271466715.07
    214 rdf:type schema:Person
    215 sg:person.01335140136.50 schema:affiliation grid-institutes:grid.417333.1
    216 schema:familyName Mochizuki
    217 schema:givenName Hitoshi
    218 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01335140136.50
    219 rdf:type schema:Person
    220 sg:person.016365545233.50 schema:affiliation grid-institutes:None
    221 schema:familyName Higuchi
    222 schema:givenName Rumi
    223 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016365545233.50
    224 rdf:type schema:Person
    225 sg:person.0605677542.20 schema:affiliation grid-institutes:None
    226 schema:familyName Goto
    227 schema:givenName Taichiro
    228 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605677542.20
    229 rdf:type schema:Person
    230 sg:person.0705402562.34 schema:affiliation grid-institutes:None
    231 schema:familyName Otake
    232 schema:givenName Sotaro
    233 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0705402562.34
    234 rdf:type schema:Person
    235 sg:person.0775700471.08 schema:affiliation grid-institutes:grid.26999.3d
    236 schema:familyName Omata
    237 schema:givenName Masao
    238 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0775700471.08
    239 rdf:type schema:Person
    240 sg:pub.10.1007/s00535-019-01547-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1111577150
    241 https://doi.org/10.1007/s00535-019-01547-z
    242 rdf:type schema:CreativeWork
    243 sg:pub.10.1007/s12032-016-0744-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1051585301
    244 https://doi.org/10.1007/s12032-016-0744-x
    245 rdf:type schema:CreativeWork
    246 sg:pub.10.1007/s12032-016-0857-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005513585
    247 https://doi.org/10.1007/s12032-016-0857-2
    248 rdf:type schema:CreativeWork
    249 sg:pub.10.1038/nature08622 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009588480
    250 https://doi.org/10.1038/nature08622
    251 rdf:type schema:CreativeWork
    252 sg:pub.10.1038/nature11156 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024120060
    253 https://doi.org/10.1038/nature11156
    254 rdf:type schema:CreativeWork
    255 sg:pub.10.1038/nature16965 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031075239
    256 https://doi.org/10.1038/nature16965
    257 rdf:type schema:CreativeWork
    258 sg:pub.10.1038/nature21063 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083822538
    259 https://doi.org/10.1038/nature21063
    260 rdf:type schema:CreativeWork
    261 sg:pub.10.1038/nbt.3520 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042966935
    262 https://doi.org/10.1038/nbt.3520
    263 rdf:type schema:CreativeWork
    264 sg:pub.10.1038/ncomms13665 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017620814
    265 https://doi.org/10.1038/ncomms13665
    266 rdf:type schema:CreativeWork
    267 sg:pub.10.1038/ng.2813 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049645772
    268 https://doi.org/10.1038/ng.2813
    269 rdf:type schema:CreativeWork
    270 sg:pub.10.1038/ng.2823 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010741940
    271 https://doi.org/10.1038/ng.2823
    272 rdf:type schema:CreativeWork
    273 sg:pub.10.1038/ng.3375 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040279504
    274 https://doi.org/10.1038/ng.3375
    275 rdf:type schema:CreativeWork
    276 sg:pub.10.1038/nm.3854 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005299046
    277 https://doi.org/10.1038/nm.3854
    278 rdf:type schema:CreativeWork
    279 sg:pub.10.1038/nrc.2017.7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083863116
    280 https://doi.org/10.1038/nrc.2017.7
    281 rdf:type schema:CreativeWork
    282 sg:pub.10.1038/nrg.2017.117 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101760979
    283 https://doi.org/10.1038/nrg.2017.117
    284 rdf:type schema:CreativeWork
    285 sg:pub.10.1186/s12864-016-3166-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039726049
    286 https://doi.org/10.1186/s12864-016-3166-4
    287 rdf:type schema:CreativeWork
    288 sg:pub.10.1186/s12885-017-3059-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053913316
    289 https://doi.org/10.1186/s12885-017-3059-1
    290 rdf:type schema:CreativeWork
    291 grid-institutes:None schema:alternateName Department of Pathology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    292 Genome Analysis Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    293 Lung Cancer and Respiratory Disease Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    294 schema:name Department of Pathology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    295 Genome Analysis Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    296 Lung Cancer and Respiratory Disease Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    297 rdf:type schema:Organization
    298 grid-institutes:grid.136304.3 schema:alternateName Department of Gastroenterology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan
    299 schema:name Department of Gastroenterology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan
    300 Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    301 rdf:type schema:Organization
    302 grid-institutes:grid.26999.3d schema:alternateName The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
    303 schema:name Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    304 The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
    305 rdf:type schema:Organization
    306 grid-institutes:grid.417333.1 schema:alternateName Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    307 schema:name Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    308 Genome Analysis Center, 1-1-1 Fujimi, Kofu, Yamanashi, Japan
    309 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...