Origin of circulating free DNA in patients with lung cancer
Liquid biopsy has become widely applied in clinical medicine along with the progress in innovative technologies, such as next generation sequencing, but the origin of circulating tumor DNA (ctDNA) has not yet been precisely established. We reported bimodal peaks of long fragment circulating free DNA...
Gespeichert in:
| Veröffentlicht in: | PloS one 2020-07, Vol.15 (7), p.e0235611-e0235611 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0235611 |
|---|---|
| container_issue | 7 |
| container_start_page | e0235611 |
| container_title | PloS one |
| container_volume | 15 |
| creator | Abe, Tomonori Nakashima, Chiho Sato, Akemi Harada, Yohei Sueoka, Eisaburo Kimura, Shinya Kawaguchi, Atsushi Sueoka-Aragane, Naoko Chalmers, Jeffrey |
| description | Liquid biopsy has become widely applied in clinical medicine along with the progress in innovative technologies, such as next generation sequencing, but the origin of circulating tumor DNA (ctDNA) has not yet been precisely established. We reported bimodal peaks of long fragment circulating free DNA (cfDNA) of 5 kb and short fragment cfDNA of 170 bp in patients with advanced lung cancer, and both contained ctDNA. In this paper, we demonstrate that the total amount of cfDNA is higher when patients with lung cancer have extrathoracic metastases, and the amount of long fragment cfDNA is significantly higher in those patients. To investigate the origin of long fragment cfDNA, conditioned media isolated from lung cancer cell lines was fractionated. Long fragment cfDNA was found concomitant with extracellular vesicles (EVs), but short fragment cfDNA was not observed in any fractions. However, in peripheral blood from a metastatic animal model both fragments were detected even with those same lung cancer cell lines. In human plasma samples, long fragment cfDNA was observed in the same fraction as that from conditioned media, and short fragment cfDNA existed in the supernatant after centrifugation at 100,000g. Concentration of ctDNA in the supernatant was two times higher than that in plasma isolated by the conventional procedure. Long fragment cfDNA associated with tumor progression might therefore be released into peripheral blood, and it is possible that the long fragment cfDNA escapes degradation by co-existing with EVs. Examination of the biological characteristics of long fragment cfDNA is a logical subject of further investigation. |
| doi_str_mv | 10.1371/journal.pone.0235611 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2421072420</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A628802106</galeid><doaj_id>oai_doaj_org_article_4aa7fb5afa8c4f529be50bf27a5ec4c1</doaj_id><sourcerecordid>A628802106</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5841-a3194d9d669e951b077f6328e8154ec122868a5b955160f02c5f8876325dda1a3</originalsourceid><addsrcrecordid>eNqNkmuL1DAUhoso7rr6DwQLguiHGXNvgiAM621gccDb13CaJp0MnWZMWi__3oxTZSv7QQJJOOc578kbTlE8xGiJaYWf78IYe-iWh9DbJSKUC4xvFedYUbIQBNHb1-5nxb2UdghxKoW4W5xRIijDVJ0XLzbRt74vgyuNj2bsYPB9W7pobfnq_arMqUMO2X5I5Xc_bMtuzGkDvbHxfnHHQZfsg-m8KD6_ef3p8t3iavN2fbm6WhguGV4AxYo1qhFCWcVxjarKCUqklZgzazAhUkjgteIcC-QQMdxJWWWENw1goBfFo5PuoQtJT76TJoxgVOUdZWJ9IpoAO32Ifg_xpw7g9e9AiK2GOHjTWc0AKldzcCANc5yo2nJUO1IBt4YZnLVeTt3Gem8bk61H6Gai80zvt7oN33RFGSJKZYGnk0AMX0ebBr33ydiug96G8fRuJhhRIqOP_0FvdjdRLWQDvnch9zVHUb0SREqUyaPW8gYqr8buvclD4nyOzwqezQoyM9gfQwtjSnr98cP_s5svc_bJNXZroRu2KXTj4EOf5iA7gSaGlKJ1fz8ZI32c8T-_oY8zrqcZp78A87Lp0w</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2421072420</pqid></control><display><type>article</type><title>Origin of circulating free DNA in patients with lung cancer</title><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Abe, Tomonori ; Nakashima, Chiho ; Sato, Akemi ; Harada, Yohei ; Sueoka, Eisaburo ; Kimura, Shinya ; Kawaguchi, Atsushi ; Sueoka-Aragane, Naoko ; Chalmers, Jeffrey</creator><contributor>Chalmers, Jeffrey</contributor><creatorcontrib>Abe, Tomonori ; Nakashima, Chiho ; Sato, Akemi ; Harada, Yohei ; Sueoka, Eisaburo ; Kimura, Shinya ; Kawaguchi, Atsushi ; Sueoka-Aragane, Naoko ; Chalmers, Jeffrey ; Chalmers, Jeffrey</creatorcontrib><description>Liquid biopsy has become widely applied in clinical medicine along with the progress in innovative technologies, such as next generation sequencing, but the origin of circulating tumor DNA (ctDNA) has not yet been precisely established. We reported bimodal peaks of long fragment circulating free DNA (cfDNA) of 5 kb and short fragment cfDNA of 170 bp in patients with advanced lung cancer, and both contained ctDNA. In this paper, we demonstrate that the total amount of cfDNA is higher when patients with lung cancer have extrathoracic metastases, and the amount of long fragment cfDNA is significantly higher in those patients. To investigate the origin of long fragment cfDNA, conditioned media isolated from lung cancer cell lines was fractionated. Long fragment cfDNA was found concomitant with extracellular vesicles (EVs), but short fragment cfDNA was not observed in any fractions. However, in peripheral blood from a metastatic animal model both fragments were detected even with those same lung cancer cell lines. In human plasma samples, long fragment cfDNA was observed in the same fraction as that from conditioned media, and short fragment cfDNA existed in the supernatant after centrifugation at 100,000g. Concentration of ctDNA in the supernatant was two times higher than that in plasma isolated by the conventional procedure. Long fragment cfDNA associated with tumor progression might therefore be released into peripheral blood, and it is possible that the long fragment cfDNA escapes degradation by co-existing with EVs. Examination of the biological characteristics of long fragment cfDNA is a logical subject of further investigation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0235611</identifier><identifier>PMID: 32634139</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Analysis ; Animal models ; Antibodies ; Biology and Life Sciences ; Biopsy ; Biotechnology ; Blood ; Blood plasma ; Capillary electrophoresis ; Carbon dioxide ; Centrifugation ; Clinical medicine ; Deoxyribonucleic acid ; Diagnosis ; DNA ; DNA sequencing ; Extracellular vesicles ; Genetic aspects ; Genetic testing ; Hematology ; Internal medicine ; Lung cancer ; Lung diseases ; Medical laboratories ; Medicine ; Medicine and Health Sciences ; Metastases ; Mutation ; Next-generation sequencing ; Oncology ; Peripheral blood ; Plasma ; Research and Analysis Methods ; Tumor cell lines ; Tumors</subject><ispartof>PloS one, 2020-07, Vol.15 (7), p.e0235611-e0235611</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Abe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Abe et al 2020 Abe et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5841-a3194d9d669e951b077f6328e8154ec122868a5b955160f02c5f8876325dda1a3</citedby><cites>FETCH-LOGICAL-c5841-a3194d9d669e951b077f6328e8154ec122868a5b955160f02c5f8876325dda1a3</cites><orcidid>0000-0002-7060-4841</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340299/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340299/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23849,27907,27908,53774,53776,79351,79352</link.rule.ids></links><search><contributor>Chalmers, Jeffrey</contributor><creatorcontrib>Abe, Tomonori</creatorcontrib><creatorcontrib>Nakashima, Chiho</creatorcontrib><creatorcontrib>Sato, Akemi</creatorcontrib><creatorcontrib>Harada, Yohei</creatorcontrib><creatorcontrib>Sueoka, Eisaburo</creatorcontrib><creatorcontrib>Kimura, Shinya</creatorcontrib><creatorcontrib>Kawaguchi, Atsushi</creatorcontrib><creatorcontrib>Sueoka-Aragane, Naoko</creatorcontrib><creatorcontrib>Chalmers, Jeffrey</creatorcontrib><title>Origin of circulating free DNA in patients with lung cancer</title><title>PloS one</title><description>Liquid biopsy has become widely applied in clinical medicine along with the progress in innovative technologies, such as next generation sequencing, but the origin of circulating tumor DNA (ctDNA) has not yet been precisely established. We reported bimodal peaks of long fragment circulating free DNA (cfDNA) of 5 kb and short fragment cfDNA of 170 bp in patients with advanced lung cancer, and both contained ctDNA. In this paper, we demonstrate that the total amount of cfDNA is higher when patients with lung cancer have extrathoracic metastases, and the amount of long fragment cfDNA is significantly higher in those patients. To investigate the origin of long fragment cfDNA, conditioned media isolated from lung cancer cell lines was fractionated. Long fragment cfDNA was found concomitant with extracellular vesicles (EVs), but short fragment cfDNA was not observed in any fractions. However, in peripheral blood from a metastatic animal model both fragments were detected even with those same lung cancer cell lines. In human plasma samples, long fragment cfDNA was observed in the same fraction as that from conditioned media, and short fragment cfDNA existed in the supernatant after centrifugation at 100,000g. Concentration of ctDNA in the supernatant was two times higher than that in plasma isolated by the conventional procedure. Long fragment cfDNA associated with tumor progression might therefore be released into peripheral blood, and it is possible that the long fragment cfDNA escapes degradation by co-existing with EVs. Examination of the biological characteristics of long fragment cfDNA is a logical subject of further investigation.</description><subject>Analysis</subject><subject>Animal models</subject><subject>Antibodies</subject><subject>Biology and Life Sciences</subject><subject>Biopsy</subject><subject>Biotechnology</subject><subject>Blood</subject><subject>Blood plasma</subject><subject>Capillary electrophoresis</subject><subject>Carbon dioxide</subject><subject>Centrifugation</subject><subject>Clinical medicine</subject><subject>Deoxyribonucleic acid</subject><subject>Diagnosis</subject><subject>DNA</subject><subject>DNA sequencing</subject><subject>Extracellular vesicles</subject><subject>Genetic aspects</subject><subject>Genetic testing</subject><subject>Hematology</subject><subject>Internal medicine</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Medical laboratories</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Mutation</subject><subject>Next-generation sequencing</subject><subject>Oncology</subject><subject>Peripheral blood</subject><subject>Plasma</subject><subject>Research and Analysis Methods</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkmuL1DAUhoso7rr6DwQLguiHGXNvgiAM621gccDb13CaJp0MnWZMWi__3oxTZSv7QQJJOOc578kbTlE8xGiJaYWf78IYe-iWh9DbJSKUC4xvFedYUbIQBNHb1-5nxb2UdghxKoW4W5xRIijDVJ0XLzbRt74vgyuNj2bsYPB9W7pobfnq_arMqUMO2X5I5Xc_bMtuzGkDvbHxfnHHQZfsg-m8KD6_ef3p8t3iavN2fbm6WhguGV4AxYo1qhFCWcVxjarKCUqklZgzazAhUkjgteIcC-QQMdxJWWWENw1goBfFo5PuoQtJT76TJoxgVOUdZWJ9IpoAO32Ifg_xpw7g9e9AiK2GOHjTWc0AKldzcCANc5yo2nJUO1IBt4YZnLVeTt3Gem8bk61H6Gai80zvt7oN33RFGSJKZYGnk0AMX0ebBr33ydiug96G8fRuJhhRIqOP_0FvdjdRLWQDvnch9zVHUb0SREqUyaPW8gYqr8buvclD4nyOzwqezQoyM9gfQwtjSnr98cP_s5svc_bJNXZroRu2KXTj4EOf5iA7gSaGlKJ1fz8ZI32c8T-_oY8zrqcZp78A87Lp0w</recordid><startdate>20200707</startdate><enddate>20200707</enddate><creator>Abe, Tomonori</creator><creator>Nakashima, Chiho</creator><creator>Sato, Akemi</creator><creator>Harada, Yohei</creator><creator>Sueoka, Eisaburo</creator><creator>Kimura, Shinya</creator><creator>Kawaguchi, Atsushi</creator><creator>Sueoka-Aragane, Naoko</creator><creator>Chalmers, Jeffrey</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7060-4841</orcidid></search><sort><creationdate>20200707</creationdate><title>Origin of circulating free DNA in patients with lung cancer</title><author>Abe, Tomonori ; Nakashima, Chiho ; Sato, Akemi ; Harada, Yohei ; Sueoka, Eisaburo ; Kimura, Shinya ; Kawaguchi, Atsushi ; Sueoka-Aragane, Naoko ; Chalmers, Jeffrey</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5841-a3194d9d669e951b077f6328e8154ec122868a5b955160f02c5f8876325dda1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>Animal models</topic><topic>Antibodies</topic><topic>Biology and Life Sciences</topic><topic>Biopsy</topic><topic>Biotechnology</topic><topic>Blood</topic><topic>Blood plasma</topic><topic>Capillary electrophoresis</topic><topic>Carbon dioxide</topic><topic>Centrifugation</topic><topic>Clinical medicine</topic><topic>Deoxyribonucleic acid</topic><topic>Diagnosis</topic><topic>DNA</topic><topic>DNA sequencing</topic><topic>Extracellular vesicles</topic><topic>Genetic aspects</topic><topic>Genetic testing</topic><topic>Hematology</topic><topic>Internal medicine</topic><topic>Lung cancer</topic><topic>Lung diseases</topic><topic>Medical laboratories</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metastases</topic><topic>Mutation</topic><topic>Next-generation sequencing</topic><topic>Oncology</topic><topic>Peripheral blood</topic><topic>Plasma</topic><topic>Research and Analysis Methods</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abe, Tomonori</creatorcontrib><creatorcontrib>Nakashima, Chiho</creatorcontrib><creatorcontrib>Sato, Akemi</creatorcontrib><creatorcontrib>Harada, Yohei</creatorcontrib><creatorcontrib>Sueoka, Eisaburo</creatorcontrib><creatorcontrib>Kimura, Shinya</creatorcontrib><creatorcontrib>Kawaguchi, Atsushi</creatorcontrib><creatorcontrib>Sueoka-Aragane, Naoko</creatorcontrib><creatorcontrib>Chalmers, Jeffrey</creatorcontrib><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abe, Tomonori</au><au>Nakashima, Chiho</au><au>Sato, Akemi</au><au>Harada, Yohei</au><au>Sueoka, Eisaburo</au><au>Kimura, Shinya</au><au>Kawaguchi, Atsushi</au><au>Sueoka-Aragane, Naoko</au><au>Chalmers, Jeffrey</au><au>Chalmers, Jeffrey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Origin of circulating free DNA in patients with lung cancer</atitle><jtitle>PloS one</jtitle><date>2020-07-07</date><risdate>2020</risdate><volume>15</volume><issue>7</issue><spage>e0235611</spage><epage>e0235611</epage><pages>e0235611-e0235611</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Liquid biopsy has become widely applied in clinical medicine along with the progress in innovative technologies, such as next generation sequencing, but the origin of circulating tumor DNA (ctDNA) has not yet been precisely established. We reported bimodal peaks of long fragment circulating free DNA (cfDNA) of 5 kb and short fragment cfDNA of 170 bp in patients with advanced lung cancer, and both contained ctDNA. In this paper, we demonstrate that the total amount of cfDNA is higher when patients with lung cancer have extrathoracic metastases, and the amount of long fragment cfDNA is significantly higher in those patients. To investigate the origin of long fragment cfDNA, conditioned media isolated from lung cancer cell lines was fractionated. Long fragment cfDNA was found concomitant with extracellular vesicles (EVs), but short fragment cfDNA was not observed in any fractions. However, in peripheral blood from a metastatic animal model both fragments were detected even with those same lung cancer cell lines. In human plasma samples, long fragment cfDNA was observed in the same fraction as that from conditioned media, and short fragment cfDNA existed in the supernatant after centrifugation at 100,000g. Concentration of ctDNA in the supernatant was two times higher than that in plasma isolated by the conventional procedure. Long fragment cfDNA associated with tumor progression might therefore be released into peripheral blood, and it is possible that the long fragment cfDNA escapes degradation by co-existing with EVs. Examination of the biological characteristics of long fragment cfDNA is a logical subject of further investigation.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>32634139</pmid><doi>10.1371/journal.pone.0235611</doi><tpages>e0235611</tpages><orcidid>https://orcid.org/0000-0002-7060-4841</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-07, Vol.15 (7), p.e0235611-e0235611 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2421072420 |
| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Animal models Antibodies Biology and Life Sciences Biopsy Biotechnology Blood Blood plasma Capillary electrophoresis Carbon dioxide Centrifugation Clinical medicine Deoxyribonucleic acid Diagnosis DNA DNA sequencing Extracellular vesicles Genetic aspects Genetic testing Hematology Internal medicine Lung cancer Lung diseases Medical laboratories Medicine Medicine and Health Sciences Metastases Mutation Next-generation sequencing Oncology Peripheral blood Plasma Research and Analysis Methods Tumor cell lines Tumors |
| title | Origin of circulating free DNA in patients with lung cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T19%3A41%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Origin%20of%20circulating%20free%20DNA%20in%20patients%20with%20lung%20cancer&rft.jtitle=PloS%20one&rft.au=Abe,%20Tomonori&rft.date=2020-07-07&rft.volume=15&rft.issue=7&rft.spage=e0235611&rft.epage=e0235611&rft.pages=e0235611-e0235611&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0235611&rft_dat=%3Cgale_plos_%3EA628802106%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2421072420&rft_id=info:pmid/32634139&rft_galeid=A628802106&rft_doaj_id=oai_doaj_org_article_4aa7fb5afa8c4f529be50bf27a5ec4c1&rfr_iscdi=true |