Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors
Identifieur interne : 000208 ( Main/Exploration ); précédent : 000207; suivant : 000209Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors
Auteurs : Joe R. Delaney [États-Unis] ; Chandni B. Patel [États-Unis] ; Jaidev Bapat [États-Unis] ; Christian M. Jones [États-Unis] ; Maria Ramos-Zapatero [États-Unis] ; Katherine K. Ortell [États-Unis] ; Ralph Tanios [États-Unis] ; Mina Haghighiabyaneh [États-Unis] ; Joshua Axelrod [États-Unis] ; John W. Destefano [États-Unis] ; Isabelle Tancioni [États-Unis] ; David D. Schlaepfer [États-Unis] ; Olivier Harismendy [États-Unis] ; Albert R. La Spada [États-Unis] ; Dwayne G. Stupack [États-Unis]Source :
- PLoS Genetics [ 1553-7390 ] ; 2020.
Abstract
Autophagy, particularly with
Url:
DOI: 10.1371/journal.pgen.1008558
PubMed: 31923184
PubMed Central: 6953790
Affiliations:
- États-Unis
- Californie, Caroline du Nord, Caroline du Sud
- Columbia (Caroline du Sud)
- Université de Caroline du Sud
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000768
- to stream Pmc, to step Curation: 000768
- to stream Pmc, to step Checkpoint: 000192
- to stream Ncbi, to step Merge: 000E22
- to stream Ncbi, to step Curation: 000E22
- to stream Ncbi, to step Checkpoint: 000E22
- to stream Main, to step Merge: 000208
- to stream Main, to step Curation: 000208
Le document en format XML
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<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>UC San Diego Moores Cancer Center, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>UC San Diego Moores Cancer Center, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Department of Pediatrics and Division of Biological Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics and Division of Biological Sciences, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jones, Christian M" sort="Jones, Christian M" uniqKey="Jones C" first="Christian M." last="Jones">Christian M. Jones</name>
<affiliation wicri:level="4"><nlm:aff id="aff004"><addr-line>Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
<settlement type="city">Columbia (Caroline du Sud)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Sud</orgName>
</affiliation>
</author>
<author><name sortKey="Ramos Zapatero, Maria" sort="Ramos Zapatero, Maria" uniqKey="Ramos Zapatero M" first="Maria" last="Ramos-Zapatero">Maria Ramos-Zapatero</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>UC San Diego Moores Cancer Center, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Department of Pediatrics and Division of Biological Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics and Division of Biological Sciences, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ortell, Katherine K" sort="Ortell, Katherine K" uniqKey="Ortell K" first="Katherine K." last="Ortell">Katherine K. Ortell</name>
<affiliation wicri:level="4"><nlm:aff id="aff004"><addr-line>Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
<settlement type="city">Columbia (Caroline du Sud)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Sud</orgName>
</affiliation>
</author>
<author><name sortKey="Tanios, Ralph" sort="Tanios, Ralph" uniqKey="Tanios R" first="Ralph" last="Tanios">Ralph Tanios</name>
<affiliation wicri:level="4"><nlm:aff id="aff004"><addr-line>Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
<settlement type="city">Columbia (Caroline du Sud)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Sud</orgName>
</affiliation>
</author>
<author><name sortKey="Haghighiabyaneh, Mina" sort="Haghighiabyaneh, Mina" uniqKey="Haghighiabyaneh M" first="Mina" last="Haghighiabyaneh">Mina Haghighiabyaneh</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>UC San Diego Moores Cancer Center, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>UC San Diego Moores Cancer Center, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Axelrod, Joshua" sort="Axelrod, Joshua" uniqKey="Axelrod J" first="Joshua" last="Axelrod">Joshua Axelrod</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>UC San Diego Moores Cancer Center, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>UC San Diego Moores Cancer Center, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Destefano, John W" sort="Destefano, John W" uniqKey="Destefano J" first="John W." last="Destefano">John W. Destefano</name>
<affiliation wicri:level="4"><nlm:aff id="aff004"><addr-line>Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Sud</region>
<settlement type="city">Columbia (Caroline du Sud)</settlement>
</placeName>
<orgName type="university">Université de Caroline du Sud</orgName>
</affiliation>
</author>
<author><name sortKey="Tancioni, Isabelle" sort="Tancioni, Isabelle" uniqKey="Tancioni I" first="Isabelle" last="Tancioni">Isabelle Tancioni</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>UC San Diego Moores Cancer Center, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>UC San Diego Moores Cancer Center, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schlaepfer, David D" sort="Schlaepfer, David D" uniqKey="Schlaepfer D" first="David D." last="Schlaepfer">David D. Schlaepfer</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>UC San Diego Moores Cancer Center, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>UC San Diego Moores Cancer Center, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Harismendy, Olivier" sort="Harismendy, Olivier" uniqKey="Harismendy O" first="Olivier" last="Harismendy">Olivier Harismendy</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>UC San Diego Moores Cancer Center, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>UC San Diego Moores Cancer Center, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff006"><addr-line>Division of Biomedical Informatics, Department of Medicine, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Biomedical Informatics, Department of Medicine, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="La Spada, Albert R" sort="La Spada, Albert R" uniqKey="La Spada A" first="Albert R." last="La Spada">Albert R. La Spada</name>
<affiliation wicri:level="2"><nlm:aff id="aff003"><addr-line>Departments of Neurology, Neurobiology, and Cell Biology, and the Duke Center for Neurodegeneration & Neurotherapeutics, Duke University School of Medicine, Durham, North Carolina, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Neurology, Neurobiology, and Cell Biology, and the Duke Center for Neurodegeneration & Neurotherapeutics, Duke University School of Medicine, Durham, North Carolina</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Department of Pediatrics and Division of Biological Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics and Division of Biological Sciences, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stupack, Dwayne G" sort="Stupack, Dwayne G" uniqKey="Stupack D" first="Dwayne G." last="Stupack">Dwayne G. Stupack</name>
<affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>UC San Diego Moores Cancer Center, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>UC San Diego Moores Cancer Center, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS Genetics</title>
<idno type="ISSN">1553-7390</idno>
<idno type="eISSN">1553-7404</idno>
<imprint><date when="2020">2020</date>
</imprint>
</series>
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<profileDesc><textClass></textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Autophagy, particularly with <italic>BECN1</italic>
, has paradoxically been highlighted as tumor promoting in Ras-driven cancers, but potentially tumor suppressing in breast and ovarian cancers. However, studying the specific role of <italic>BECN1</italic>
at the genetic level is complicated due to its genomic proximity to <italic>BRCA1</italic>
on both human (chromosome 17) and murine (chromosome 11) genomes. In human breast and ovarian cancers, the monoallelic deletion of these genes is often co-occurring. To investigate the potential tumor suppressor roles of two of the most commonly deleted autophagy genes in ovarian cancer, <italic>BECN1</italic>
and <italic>MAP1LC3B</italic>
were knocked-down in atypical (<italic>BECN1</italic>
+/+ and <italic>MAP1LC3B</italic>
+/+) ovarian cancer cells. Ultra-performance liquid chromatography mass-spectrometry metabolomics revealed reduced levels of acetyl-CoA which corresponded with elevated levels of glycerophospholipids and sphingolipids. Migration rates of ovarian cancer cells were increased upon autophagy gene knockdown. Genomic instability was increased, resulting in copy-number alteration patterns which mimicked high grade serous ovarian cancer. We further investigated the causal role of <italic>Becn1</italic>
haploinsufficiency for oncogenesis in a MISIIR SV40 large T antigen driven spontaneous ovarian cancer mouse model. Tumors were evident earlier among the <italic>Becn1</italic>
+/- mice, and this correlated with an increase in copy-number alterations per chromosome in the <italic>Becn1</italic>
+/- tumors. The results support monoallelic loss of <italic>BECN1</italic>
as permissive for tumor initiation and potentiating for genomic instability in ovarian cancer.</p>
</div>
</front>
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</analytic>
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</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Caroline du Nord</li>
<li>Caroline du Sud</li>
</region>
<settlement><li>Columbia (Caroline du Sud)</li>
</settlement>
<orgName><li>Université de Caroline du Sud</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Californie"><name sortKey="Delaney, Joe R" sort="Delaney, Joe R" uniqKey="Delaney J" first="Joe R." last="Delaney">Joe R. Delaney</name>
</region>
<name sortKey="Axelrod, Joshua" sort="Axelrod, Joshua" uniqKey="Axelrod J" first="Joshua" last="Axelrod">Joshua Axelrod</name>
<name sortKey="Axelrod, Joshua" sort="Axelrod, Joshua" uniqKey="Axelrod J" first="Joshua" last="Axelrod">Joshua Axelrod</name>
<name sortKey="Bapat, Jaidev" sort="Bapat, Jaidev" uniqKey="Bapat J" first="Jaidev" last="Bapat">Jaidev Bapat</name>
<name sortKey="Bapat, Jaidev" sort="Bapat, Jaidev" uniqKey="Bapat J" first="Jaidev" last="Bapat">Jaidev Bapat</name>
<name sortKey="Bapat, Jaidev" sort="Bapat, Jaidev" uniqKey="Bapat J" first="Jaidev" last="Bapat">Jaidev Bapat</name>
<name sortKey="Delaney, Joe R" sort="Delaney, Joe R" uniqKey="Delaney J" first="Joe R." last="Delaney">Joe R. Delaney</name>
<name sortKey="Delaney, Joe R" sort="Delaney, Joe R" uniqKey="Delaney J" first="Joe R." last="Delaney">Joe R. Delaney</name>
<name sortKey="Delaney, Joe R" sort="Delaney, Joe R" uniqKey="Delaney J" first="Joe R." last="Delaney">Joe R. Delaney</name>
<name sortKey="Delaney, Joe R" sort="Delaney, Joe R" uniqKey="Delaney J" first="Joe R." last="Delaney">Joe R. Delaney</name>
<name sortKey="Destefano, John W" sort="Destefano, John W" uniqKey="Destefano J" first="John W." last="Destefano">John W. Destefano</name>
<name sortKey="Haghighiabyaneh, Mina" sort="Haghighiabyaneh, Mina" uniqKey="Haghighiabyaneh M" first="Mina" last="Haghighiabyaneh">Mina Haghighiabyaneh</name>
<name sortKey="Haghighiabyaneh, Mina" sort="Haghighiabyaneh, Mina" uniqKey="Haghighiabyaneh M" first="Mina" last="Haghighiabyaneh">Mina Haghighiabyaneh</name>
<name sortKey="Harismendy, Olivier" sort="Harismendy, Olivier" uniqKey="Harismendy O" first="Olivier" last="Harismendy">Olivier Harismendy</name>
<name sortKey="Harismendy, Olivier" sort="Harismendy, Olivier" uniqKey="Harismendy O" first="Olivier" last="Harismendy">Olivier Harismendy</name>
<name sortKey="Jones, Christian M" sort="Jones, Christian M" uniqKey="Jones C" first="Christian M." last="Jones">Christian M. Jones</name>
<name sortKey="La Spada, Albert R" sort="La Spada, Albert R" uniqKey="La Spada A" first="Albert R." last="La Spada">Albert R. La Spada</name>
<name sortKey="La Spada, Albert R" sort="La Spada, Albert R" uniqKey="La Spada A" first="Albert R." last="La Spada">Albert R. La Spada</name>
<name sortKey="Ortell, Katherine K" sort="Ortell, Katherine K" uniqKey="Ortell K" first="Katherine K." last="Ortell">Katherine K. Ortell</name>
<name sortKey="Patel, Chandni B" sort="Patel, Chandni B" uniqKey="Patel C" first="Chandni B." last="Patel">Chandni B. Patel</name>
<name sortKey="Patel, Chandni B" sort="Patel, Chandni B" uniqKey="Patel C" first="Chandni B." last="Patel">Chandni B. Patel</name>
<name sortKey="Ramos Zapatero, Maria" sort="Ramos Zapatero, Maria" uniqKey="Ramos Zapatero M" first="Maria" last="Ramos-Zapatero">Maria Ramos-Zapatero</name>
<name sortKey="Ramos Zapatero, Maria" sort="Ramos Zapatero, Maria" uniqKey="Ramos Zapatero M" first="Maria" last="Ramos-Zapatero">Maria Ramos-Zapatero</name>
<name sortKey="Ramos Zapatero, Maria" sort="Ramos Zapatero, Maria" uniqKey="Ramos Zapatero M" first="Maria" last="Ramos-Zapatero">Maria Ramos-Zapatero</name>
<name sortKey="Schlaepfer, David D" sort="Schlaepfer, David D" uniqKey="Schlaepfer D" first="David D." last="Schlaepfer">David D. Schlaepfer</name>
<name sortKey="Schlaepfer, David D" sort="Schlaepfer, David D" uniqKey="Schlaepfer D" first="David D." last="Schlaepfer">David D. Schlaepfer</name>
<name sortKey="Stupack, Dwayne G" sort="Stupack, Dwayne G" uniqKey="Stupack D" first="Dwayne G." last="Stupack">Dwayne G. Stupack</name>
<name sortKey="Stupack, Dwayne G" sort="Stupack, Dwayne G" uniqKey="Stupack D" first="Dwayne G." last="Stupack">Dwayne G. Stupack</name>
<name sortKey="Tancioni, Isabelle" sort="Tancioni, Isabelle" uniqKey="Tancioni I" first="Isabelle" last="Tancioni">Isabelle Tancioni</name>
<name sortKey="Tancioni, Isabelle" sort="Tancioni, Isabelle" uniqKey="Tancioni I" first="Isabelle" last="Tancioni">Isabelle Tancioni</name>
<name sortKey="Tanios, Ralph" sort="Tanios, Ralph" uniqKey="Tanios R" first="Ralph" last="Tanios">Ralph Tanios</name>
</country>
</tree>
</affiliations>
</record>
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