Serveur d'exploration Chloroquine

Attention, ce site est en cours de développement !
Attention, site généré par des moyens informatiques à partir de corpus bruts.
Les informations ne sont donc pas validées.

Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors

Identifieur interne : 000192 ( Pmc/Checkpoint ); précédent : 000191; suivant : 000193

Autophagy 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 :

RBID : PMC:6953790

Abstract

Autophagy, particularly with BECN1, 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 BECN1 at the genetic level is complicated due to its genomic proximity to BRCA1 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, BECN1 and MAP1LC3B were knocked-down in atypical (BECN1+/+ and MAP1LC3B+/+) 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 Becn1 haploinsufficiency for oncogenesis in a MISIIR SV40 large T antigen driven spontaneous ovarian cancer mouse model. Tumors were evident earlier among the Becn1+/- mice, and this correlated with an increase in copy-number alterations per chromosome in the Becn1+/- tumors. The results support monoallelic loss of BECN1 as permissive for tumor initiation and potentiating for genomic instability in ovarian cancer.


Url:
DOI: 10.1371/journal.pgen.1008558
PubMed: 31923184
PubMed Central: 6953790


Affiliations:


Links toward previous steps (curation, corpus...)


Links to Exploration step

PMC:6953790

Le document en format XML

<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors</title>
<author>
<name sortKey="Delaney, Joe R" sort="Delaney, Joe R" uniqKey="Delaney J" first="Joe R." last="Delaney">Joe R. Delaney</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>
<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="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>
<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="Patel, Chandni B" sort="Patel, Chandni B" uniqKey="Patel C" first="Chandni B." last="Patel">Chandni B. Patel</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="Bapat, Jaidev" sort="Bapat, Jaidev" uniqKey="Bapat J" first="Jaidev" last="Bapat">Jaidev Bapat</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>
<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>
<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="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>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">31923184</idno>
<idno type="pmc">6953790</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953790</idno>
<idno type="RBID">PMC:6953790</idno>
<idno type="doi">10.1371/journal.pgen.1008558</idno>
<date when="2020">2020</date>
<idno type="wicri:Area/Pmc/Corpus">000768</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000768</idno>
<idno type="wicri:Area/Pmc/Curation">000768</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000768</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000192</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000192</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en" level="a" type="main">Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors</title>
<author>
<name sortKey="Delaney, Joe R" sort="Delaney, Joe R" uniqKey="Delaney J" first="Joe R." last="Delaney">Joe R. Delaney</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>
<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="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>
<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="Patel, Chandni B" sort="Patel, Chandni B" uniqKey="Patel C" first="Chandni B." last="Patel">Chandni B. Patel</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="Bapat, Jaidev" sort="Bapat, Jaidev" uniqKey="Bapat J" first="Jaidev" last="Bapat">Jaidev Bapat</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>
<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>
<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="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>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</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>
<back>
<div1 type="bibliography">
<listBibl>
<biblStruct>
<analytic>
<author>
<name sortKey="Levine, B" uniqKey="Levine B">B Levine</name>
</author>
<author>
<name sortKey="Kroemer, G" uniqKey="Kroemer G">G Kroemer</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Guo, Jy" uniqKey="Guo J">JY Guo</name>
</author>
<author>
<name sortKey="Chen, Hy" uniqKey="Chen H">HY Chen</name>
</author>
<author>
<name sortKey="Mathew, R" uniqKey="Mathew R">R Mathew</name>
</author>
<author>
<name sortKey="Fan, J" uniqKey="Fan J">J Fan</name>
</author>
<author>
<name sortKey="Strohecker, Am" uniqKey="Strohecker A">AM Strohecker</name>
</author>
<author>
<name sortKey="Karsli Uzunbas, G" uniqKey="Karsli Uzunbas G">G Karsli-Uzunbas</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Karsli Uzunbas, G" uniqKey="Karsli Uzunbas G">G Karsli-Uzunbas</name>
</author>
<author>
<name sortKey="Guo, Jy" uniqKey="Guo J">JY Guo</name>
</author>
<author>
<name sortKey="Price, S" uniqKey="Price S">S Price</name>
</author>
<author>
<name sortKey="Teng, X" uniqKey="Teng X">X Teng</name>
</author>
<author>
<name sortKey="Laddha, Sv" uniqKey="Laddha S">SV Laddha</name>
</author>
<author>
<name sortKey="Khor, S" uniqKey="Khor S">S Khor</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Strohecker, Am" uniqKey="Strohecker A">AM Strohecker</name>
</author>
<author>
<name sortKey="Guo, Jy" uniqKey="Guo J">JY Guo</name>
</author>
<author>
<name sortKey="Karsli Uzunbas, G" uniqKey="Karsli Uzunbas G">G Karsli-Uzunbas</name>
</author>
<author>
<name sortKey="Price, Sm" uniqKey="Price S">SM Price</name>
</author>
<author>
<name sortKey="Chen, Gj" uniqKey="Chen G">GJ Chen</name>
</author>
<author>
<name sortKey="Mathew, R" uniqKey="Mathew R">R Mathew</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Guo, Jy" uniqKey="Guo J">JY Guo</name>
</author>
<author>
<name sortKey="Teng, X" uniqKey="Teng X">X Teng</name>
</author>
<author>
<name sortKey="Laddha, Sv" uniqKey="Laddha S">SV Laddha</name>
</author>
<author>
<name sortKey="Ma, S" uniqKey="Ma S">S Ma</name>
</author>
<author>
<name sortKey="Van Nostrand, Sc" uniqKey="Van Nostrand S">SC Van Nostrand</name>
</author>
<author>
<name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Liu, Ey" uniqKey="Liu E">EY Liu</name>
</author>
<author>
<name sortKey="Xu, N" uniqKey="Xu N">N Xu</name>
</author>
<author>
<name sortKey="O Prey, J" uniqKey="O Prey J">J O'Prey</name>
</author>
<author>
<name sortKey="Lao, Ly" uniqKey="Lao L">LY Lao</name>
</author>
<author>
<name sortKey="Joshi, S" uniqKey="Joshi S">S Joshi</name>
</author>
<author>
<name sortKey="Long, Js" uniqKey="Long J">JS Long</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Qiang, L" uniqKey="Qiang L">L Qiang</name>
</author>
<author>
<name sortKey="Zhao, B" uniqKey="Zhao B">B Zhao</name>
</author>
<author>
<name sortKey="Shah, P" uniqKey="Shah P">P Shah</name>
</author>
<author>
<name sortKey="Sample, A" uniqKey="Sample A">A Sample</name>
</author>
<author>
<name sortKey="Yang, S" uniqKey="Yang S">S Yang</name>
</author>
<author>
<name sortKey="He, Yy" uniqKey="He Y">YY He</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Hewitt, G" uniqKey="Hewitt G">G Hewitt</name>
</author>
<author>
<name sortKey="Carroll, B" uniqKey="Carroll B">B Carroll</name>
</author>
<author>
<name sortKey="Sarallah, R" uniqKey="Sarallah R">R Sarallah</name>
</author>
<author>
<name sortKey="Correia Melo, C" uniqKey="Correia Melo C">C Correia-Melo</name>
</author>
<author>
<name sortKey="Ogrodnik, M" uniqKey="Ogrodnik M">M Ogrodnik</name>
</author>
<author>
<name sortKey="Nelson, G" uniqKey="Nelson G">G Nelson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Klionsky, Dj" uniqKey="Klionsky D">DJ Klionsky</name>
</author>
<author>
<name sortKey="Abdelmohsen, K" uniqKey="Abdelmohsen K">K Abdelmohsen</name>
</author>
<author>
<name sortKey="Abe, A" uniqKey="Abe A">A Abe</name>
</author>
<author>
<name sortKey="Abedin, Mj" uniqKey="Abedin M">MJ Abedin</name>
</author>
<author>
<name sortKey="Abeliovich, H" uniqKey="Abeliovich H">H Abeliovich</name>
</author>
<author>
<name sortKey="Acevedo Arozena, A" uniqKey="Acevedo Arozena A">A Acevedo Arozena</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Qu, X" uniqKey="Qu X">X Qu</name>
</author>
<author>
<name sortKey="Yu, J" uniqKey="Yu J">J Yu</name>
</author>
<author>
<name sortKey="Bhagat, G" uniqKey="Bhagat G">G Bhagat</name>
</author>
<author>
<name sortKey="Furuya, N" uniqKey="Furuya N">N Furuya</name>
</author>
<author>
<name sortKey="Hibshoosh, H" uniqKey="Hibshoosh H">H Hibshoosh</name>
</author>
<author>
<name sortKey="Troxel, A" uniqKey="Troxel A">A Troxel</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Yue, Z" uniqKey="Yue Z">Z Yue</name>
</author>
<author>
<name sortKey="Jin, S" uniqKey="Jin S">S Jin</name>
</author>
<author>
<name sortKey="Yang, C" uniqKey="Yang C">C Yang</name>
</author>
<author>
<name sortKey="Levine, Aj" uniqKey="Levine A">AJ Levine</name>
</author>
<author>
<name sortKey="Heintz, N" uniqKey="Heintz N">N Heintz</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Laddha, Sv" uniqKey="Laddha S">SV Laddha</name>
</author>
<author>
<name sortKey="Ganesan, S" uniqKey="Ganesan S">S Ganesan</name>
</author>
<author>
<name sortKey="Chan, Cs" uniqKey="Chan C">CS Chan</name>
</author>
<author>
<name sortKey="White, E" uniqKey="White E">E White</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name>
</author>
<author>
<name sortKey="Chen, C" uniqKey="Chen C">C Chen</name>
</author>
<author>
<name sortKey="Xu, Z" uniqKey="Xu Z">Z Xu</name>
</author>
<author>
<name sortKey="Scuoppo, C" uniqKey="Scuoppo C">C Scuoppo</name>
</author>
<author>
<name sortKey="Rillahan, Cd" uniqKey="Rillahan C">CD Rillahan</name>
</author>
<author>
<name sortKey="Gao, J" uniqKey="Gao J">J Gao</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Tang, H" uniqKey="Tang H">H Tang</name>
</author>
<author>
<name sortKey="Sebti, S" uniqKey="Sebti S">S Sebti</name>
</author>
<author>
<name sortKey="Titone, R" uniqKey="Titone R">R Titone</name>
</author>
<author>
<name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name>
</author>
<author>
<name sortKey="Isidoro, C" uniqKey="Isidoro C">C Isidoro</name>
</author>
<author>
<name sortKey="Ross, Ts" uniqKey="Ross T">TS Ross</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Liang, Xh" uniqKey="Liang X">XH Liang</name>
</author>
<author>
<name sortKey="Jackson, S" uniqKey="Jackson S">S Jackson</name>
</author>
<author>
<name sortKey="Seaman, M" uniqKey="Seaman M">M Seaman</name>
</author>
<author>
<name sortKey="Brown, K" uniqKey="Brown K">K Brown</name>
</author>
<author>
<name sortKey="Kempkes, B" uniqKey="Kempkes B">B Kempkes</name>
</author>
<author>
<name sortKey="Hibshoosh, H" uniqKey="Hibshoosh H">H Hibshoosh</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Delaney, Jr" uniqKey="Delaney J">JR Delaney</name>
</author>
<author>
<name sortKey="Patel, Cb" uniqKey="Patel C">CB Patel</name>
</author>
<author>
<name sortKey="Willis, Km" uniqKey="Willis K">KM Willis</name>
</author>
<author>
<name sortKey="Haghighiabyaneh, M" uniqKey="Haghighiabyaneh M">M Haghighiabyaneh</name>
</author>
<author>
<name sortKey="Axelrod, J" uniqKey="Axelrod J">J Axelrod</name>
</author>
<author>
<name sortKey="Tancioni, I" uniqKey="Tancioni I">I Tancioni</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Delaney, Jr" uniqKey="Delaney J">JR Delaney</name>
</author>
<author>
<name sortKey="Patel, C" uniqKey="Patel C">C Patel</name>
</author>
<author>
<name sortKey="Mccabe, Ke" uniqKey="Mccabe K">KE McCabe</name>
</author>
<author>
<name sortKey="Lu, D" uniqKey="Lu D">D Lu</name>
</author>
<author>
<name sortKey="Davis, Ma" uniqKey="Davis M">MA Davis</name>
</author>
<author>
<name sortKey="Tancioni, I" uniqKey="Tancioni I">I Tancioni</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Andor, N" uniqKey="Andor N">N Andor</name>
</author>
<author>
<name sortKey="Graham, Ta" uniqKey="Graham T">TA Graham</name>
</author>
<author>
<name sortKey="Jansen, M" uniqKey="Jansen M">M Jansen</name>
</author>
<author>
<name sortKey="Xia, Lc" uniqKey="Xia L">LC Xia</name>
</author>
<author>
<name sortKey="Aktipis, Ca" uniqKey="Aktipis C">CA Aktipis</name>
</author>
<author>
<name sortKey="Petritsch, C" uniqKey="Petritsch C">C Petritsch</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Raynaud, F" uniqKey="Raynaud F">F Raynaud</name>
</author>
<author>
<name sortKey="Mina, M" uniqKey="Mina M">M Mina</name>
</author>
<author>
<name sortKey="Tavernari, D" uniqKey="Tavernari D">D Tavernari</name>
</author>
<author>
<name sortKey="Ciriello, G" uniqKey="Ciriello G">G Ciriello</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Gao, J" uniqKey="Gao J">J Gao</name>
</author>
<author>
<name sortKey="Aksoy, Ba" uniqKey="Aksoy B">BA Aksoy</name>
</author>
<author>
<name sortKey="Dogrusoz, U" uniqKey="Dogrusoz U">U Dogrusoz</name>
</author>
<author>
<name sortKey="Dresdner, G" uniqKey="Dresdner G">G Dresdner</name>
</author>
<author>
<name sortKey="Gross, B" uniqKey="Gross B">B Gross</name>
</author>
<author>
<name sortKey="Sumer, So" uniqKey="Sumer S">SO Sumer</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Davoli, T" uniqKey="Davoli T">T Davoli</name>
</author>
<author>
<name sortKey="Xu, Aw" uniqKey="Xu A">AW Xu</name>
</author>
<author>
<name sortKey="Mengwasser, Ke" uniqKey="Mengwasser K">KE Mengwasser</name>
</author>
<author>
<name sortKey="Sack, Lm" uniqKey="Sack L">LM Sack</name>
</author>
<author>
<name sortKey="Yoon, Jc" uniqKey="Yoon J">JC Yoon</name>
</author>
<author>
<name sortKey="Park, Pj" uniqKey="Park P">PJ Park</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Sack, Lm" uniqKey="Sack L">LM Sack</name>
</author>
<author>
<name sortKey="Davoli, T" uniqKey="Davoli T">T Davoli</name>
</author>
<author>
<name sortKey="Li, Mz" uniqKey="Li M">MZ Li</name>
</author>
<author>
<name sortKey="Li, Y" uniqKey="Li Y">Y Li</name>
</author>
<author>
<name sortKey="Xu, Q" uniqKey="Xu Q">Q Xu</name>
</author>
<author>
<name sortKey="Naxerova, K" uniqKey="Naxerova K">K Naxerova</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Xu, B" uniqKey="Xu B">B Xu</name>
</author>
<author>
<name sortKey="Lefringhouse, J" uniqKey="Lefringhouse J">J Lefringhouse</name>
</author>
<author>
<name sortKey="Liu, Z" uniqKey="Liu Z">Z Liu</name>
</author>
<author>
<name sortKey="West, D" uniqKey="West D">D West</name>
</author>
<author>
<name sortKey="Baldwin, La" uniqKey="Baldwin L">LA Baldwin</name>
</author>
<author>
<name sortKey="Ou, C" uniqKey="Ou C">C Ou</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Hernandez, L" uniqKey="Hernandez L">L Hernandez</name>
</author>
<author>
<name sortKey="Kim, Mk" uniqKey="Kim M">MK Kim</name>
</author>
<author>
<name sortKey="Lyle, Lt" uniqKey="Lyle L">LT Lyle</name>
</author>
<author>
<name sortKey="Bunch, Kp" uniqKey="Bunch K">KP Bunch</name>
</author>
<author>
<name sortKey="House, Cd" uniqKey="House C">CD House</name>
</author>
<author>
<name sortKey="Ning, F" uniqKey="Ning F">F Ning</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Correa, Rj" uniqKey="Correa R">RJ Correa</name>
</author>
<author>
<name sortKey="Valdes, Yr" uniqKey="Valdes Y">YR Valdes</name>
</author>
<author>
<name sortKey="Shepherd, Tg" uniqKey="Shepherd T">TG Shepherd</name>
</author>
<author>
<name sortKey="Dimattia, Ge" uniqKey="Dimattia G">GE DiMattia</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Dolce, V" uniqKey="Dolce V">V Dolce</name>
</author>
<author>
<name sortKey="Cappello, Ar" uniqKey="Cappello A">AR Cappello</name>
</author>
<author>
<name sortKey="Lappano, R" uniqKey="Lappano R">R Lappano</name>
</author>
<author>
<name sortKey="Maggiolini, M" uniqKey="Maggiolini M">M Maggiolini</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Sharifi, Mn" uniqKey="Sharifi M">MN Sharifi</name>
</author>
<author>
<name sortKey="Mowers, Ee" uniqKey="Mowers E">EE Mowers</name>
</author>
<author>
<name sortKey="Drake, Le" uniqKey="Drake L">LE Drake</name>
</author>
<author>
<name sortKey="Collier, C" uniqKey="Collier C">C Collier</name>
</author>
<author>
<name sortKey="Chen, H" uniqKey="Chen H">H Chen</name>
</author>
<author>
<name sortKey="Zamora, M" uniqKey="Zamora M">M Zamora</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kenific, Cm" uniqKey="Kenific C">CM Kenific</name>
</author>
<author>
<name sortKey="Wittmann, T" uniqKey="Wittmann T">T Wittmann</name>
</author>
<author>
<name sortKey="Debnath, J" uniqKey="Debnath J">J Debnath</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Hanahan, D" uniqKey="Hanahan D">D Hanahan</name>
</author>
<author>
<name sortKey="Weinberg, Ra" uniqKey="Weinberg R">RA Weinberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Collins, Ar" uniqKey="Collins A">AR Collins</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Watanabe, Y" uniqKey="Watanabe Y">Y Watanabe</name>
</author>
<author>
<name sortKey="Honda, S" uniqKey="Honda S">S Honda</name>
</author>
<author>
<name sortKey="Konishi, A" uniqKey="Konishi A">A Konishi</name>
</author>
<author>
<name sortKey="Arakawa, S" uniqKey="Arakawa S">S Arakawa</name>
</author>
<author>
<name sortKey="Murohashi, M" uniqKey="Murohashi M">M Murohashi</name>
</author>
<author>
<name sortKey="Yamaguchi, H" uniqKey="Yamaguchi H">H Yamaguchi</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Foster, Jm" uniqKey="Foster J">JM Foster</name>
</author>
<author>
<name sortKey="Oumie, A" uniqKey="Oumie A">A Oumie</name>
</author>
<author>
<name sortKey="Togneri, Fs" uniqKey="Togneri F">FS Togneri</name>
</author>
<author>
<name sortKey="Vasques, Fr" uniqKey="Vasques F">FR Vasques</name>
</author>
<author>
<name sortKey="Hau, D" uniqKey="Hau D">D Hau</name>
</author>
<author>
<name sortKey="Taylor, M" uniqKey="Taylor M">M Taylor</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Olshen, Ab" uniqKey="Olshen A">AB Olshen</name>
</author>
<author>
<name sortKey="Venkatraman, Es" uniqKey="Venkatraman E">ES Venkatraman</name>
</author>
<author>
<name sortKey="Lucito, R" uniqKey="Lucito R">R Lucito</name>
</author>
<author>
<name sortKey="Wigler, M" uniqKey="Wigler M">M Wigler</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Mathew, R" uniqKey="Mathew R">R Mathew</name>
</author>
<author>
<name sortKey="Kongara, S" uniqKey="Kongara S">S Kongara</name>
</author>
<author>
<name sortKey="Beaudoin, B" uniqKey="Beaudoin B">B Beaudoin</name>
</author>
<author>
<name sortKey="Karp, Cm" uniqKey="Karp C">CM Karp</name>
</author>
<author>
<name sortKey="Bray, K" uniqKey="Bray K">K Bray</name>
</author>
<author>
<name sortKey="Degenhardt, K" uniqKey="Degenhardt K">K Degenhardt</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Fremont, S" uniqKey="Fremont S">S Fremont</name>
</author>
<author>
<name sortKey="Gerard, A" uniqKey="Gerard A">A Gerard</name>
</author>
<author>
<name sortKey="Galloux, M" uniqKey="Galloux M">M Galloux</name>
</author>
<author>
<name sortKey="Janvier, K" uniqKey="Janvier K">K Janvier</name>
</author>
<author>
<name sortKey="Karess, Re" uniqKey="Karess R">RE Karess</name>
</author>
<author>
<name sortKey="Berlioz Torrent, C" uniqKey="Berlioz Torrent C">C Berlioz-Torrent</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Wei, Pc" uniqKey="Wei P">PC Wei</name>
</author>
<author>
<name sortKey="Chang, An" uniqKey="Chang A">AN Chang</name>
</author>
<author>
<name sortKey="Kao, J" uniqKey="Kao J">J Kao</name>
</author>
<author>
<name sortKey="Du, Z" uniqKey="Du Z">Z Du</name>
</author>
<author>
<name sortKey="Meyers, Rm" uniqKey="Meyers R">RM Meyers</name>
</author>
<author>
<name sortKey="Alt, Fw" uniqKey="Alt F">FW Alt</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Mootha, Vk" uniqKey="Mootha V">VK Mootha</name>
</author>
<author>
<name sortKey="Lindgren, Cm" uniqKey="Lindgren C">CM Lindgren</name>
</author>
<author>
<name sortKey="Eriksson, Kf" uniqKey="Eriksson K">KF Eriksson</name>
</author>
<author>
<name sortKey="Subramanian, A" uniqKey="Subramanian A">A Subramanian</name>
</author>
<author>
<name sortKey="Sihag, S" uniqKey="Sihag S">S Sihag</name>
</author>
<author>
<name sortKey="Lehar, J" uniqKey="Lehar J">J Lehar</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Marks, Jr" uniqKey="Marks J">JR Marks</name>
</author>
<author>
<name sortKey="Davidoff, Am" uniqKey="Davidoff A">AM Davidoff</name>
</author>
<author>
<name sortKey="Kerns, Bj" uniqKey="Kerns B">BJ Kerns</name>
</author>
<author>
<name sortKey="Humphrey, Pa" uniqKey="Humphrey P">PA Humphrey</name>
</author>
<author>
<name sortKey="Pence, Jc" uniqKey="Pence J">JC Pence</name>
</author>
<author>
<name sortKey="Dodge, Rk" uniqKey="Dodge R">RK Dodge</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Schwarz, Rf" uniqKey="Schwarz R">RF Schwarz</name>
</author>
<author>
<name sortKey="Ng, Ck" uniqKey="Ng C">CK Ng</name>
</author>
<author>
<name sortKey="Cooke, Sl" uniqKey="Cooke S">SL Cooke</name>
</author>
<author>
<name sortKey="Newman, S" uniqKey="Newman S">S Newman</name>
</author>
<author>
<name sortKey="Temple, J" uniqKey="Temple J">J Temple</name>
</author>
<author>
<name sortKey="Piskorz, Am" uniqKey="Piskorz A">AM Piskorz</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ali, Sh" uniqKey="Ali S">SH Ali</name>
</author>
<author>
<name sortKey="Decaprio, Ja" uniqKey="Decaprio J">JA DeCaprio</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Hensley, H" uniqKey="Hensley H">H Hensley</name>
</author>
<author>
<name sortKey="Quinn, Ba" uniqKey="Quinn B">BA Quinn</name>
</author>
<author>
<name sortKey="Wolf, Rl" uniqKey="Wolf R">RL Wolf</name>
</author>
<author>
<name sortKey="Litwin, Sl" uniqKey="Litwin S">SL Litwin</name>
</author>
<author>
<name sortKey="Mabuchi, S" uniqKey="Mabuchi S">S Mabuchi</name>
</author>
<author>
<name sortKey="Williams, Sj" uniqKey="Williams S">SJ Williams</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Harter, P" uniqKey="Harter P">P Harter</name>
</author>
<author>
<name sortKey="Hauke, J" uniqKey="Hauke J">J Hauke</name>
</author>
<author>
<name sortKey="Heitz, F" uniqKey="Heitz F">F Heitz</name>
</author>
<author>
<name sortKey="Reuss, A" uniqKey="Reuss A">A Reuss</name>
</author>
<author>
<name sortKey="Kommoss, S" uniqKey="Kommoss S">S Kommoss</name>
</author>
<author>
<name sortKey="Marme, F" uniqKey="Marme F">F Marme</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="White, E" uniqKey="White E">E. White</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Silver, Dp" uniqKey="Silver D">DP Silver</name>
</author>
<author>
<name sortKey="Livingston, Dm" uniqKey="Livingston D">DM Livingston</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lengyel, E" uniqKey="Lengyel E">E. Lengyel</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Eckert, Ma" uniqKey="Eckert M">MA Eckert</name>
</author>
<author>
<name sortKey="Pan, S" uniqKey="Pan S">S Pan</name>
</author>
<author>
<name sortKey="Hernandez, Km" uniqKey="Hernandez K">KM Hernandez</name>
</author>
<author>
<name sortKey="Loth, Rm" uniqKey="Loth R">RM Loth</name>
</author>
<author>
<name sortKey="Andrade, J" uniqKey="Andrade J">J Andrade</name>
</author>
<author>
<name sortKey="Volchenboum, Sl" uniqKey="Volchenboum S">SL Volchenboum</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Oren, M" uniqKey="Oren M">M Oren</name>
</author>
<author>
<name sortKey="Rotter, V" uniqKey="Rotter V">V Rotter</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Cole, Aj" uniqKey="Cole A">AJ Cole</name>
</author>
<author>
<name sortKey="Dwight, T" uniqKey="Dwight T">T Dwight</name>
</author>
<author>
<name sortKey="Gill, Aj" uniqKey="Gill A">AJ Gill</name>
</author>
<author>
<name sortKey="Dickson, Ka" uniqKey="Dickson K">KA Dickson</name>
</author>
<author>
<name sortKey="Zhu, Y" uniqKey="Zhu Y">Y Zhu</name>
</author>
<author>
<name sortKey="Clarkson, A" uniqKey="Clarkson A">A Clarkson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Cicchini, M" uniqKey="Cicchini M">M Cicchini</name>
</author>
<author>
<name sortKey="Chakrabarti, R" uniqKey="Chakrabarti R">R Chakrabarti</name>
</author>
<author>
<name sortKey="Kongara, S" uniqKey="Kongara S">S Kongara</name>
</author>
<author>
<name sortKey="Price, S" uniqKey="Price S">S Price</name>
</author>
<author>
<name sortKey="Nahar, R" uniqKey="Nahar R">R Nahar</name>
</author>
<author>
<name sortKey="Lozy, F" uniqKey="Lozy F">F Lozy</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Wang, Yk" uniqKey="Wang Y">YK Wang</name>
</author>
<author>
<name sortKey="Bashashati, A" uniqKey="Bashashati A">A Bashashati</name>
</author>
<author>
<name sortKey="Anglesio, Ms" uniqKey="Anglesio M">MS Anglesio</name>
</author>
<author>
<name sortKey="Cochrane, Dr" uniqKey="Cochrane D">DR Cochrane</name>
</author>
<author>
<name sortKey="Grewal, Ds" uniqKey="Grewal D">DS Grewal</name>
</author>
<author>
<name sortKey="Ha, G" uniqKey="Ha G">G Ha</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lemasters, Jj" uniqKey="Lemasters J">JJ Lemasters</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Jena, Nr" uniqKey="Jena N">NR Jena</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Behrends, C" uniqKey="Behrends C">C Behrends</name>
</author>
<author>
<name sortKey="Sowa, Me" uniqKey="Sowa M">ME Sowa</name>
</author>
<author>
<name sortKey="Gygi, Sp" uniqKey="Gygi S">SP Gygi</name>
</author>
<author>
<name sortKey="Harper, Jw" uniqKey="Harper J">JW Harper</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Koukourakis, Mi" uniqKey="Koukourakis M">MI Koukourakis</name>
</author>
<author>
<name sortKey="Kalamida, D" uniqKey="Kalamida D">D Kalamida</name>
</author>
<author>
<name sortKey="Giatromanolaki, A" uniqKey="Giatromanolaki A">A Giatromanolaki</name>
</author>
<author>
<name sortKey="Zois, Ce" uniqKey="Zois C">CE Zois</name>
</author>
<author>
<name sortKey="Sivridis, E" uniqKey="Sivridis E">E Sivridis</name>
</author>
<author>
<name sortKey="Pouliliou, S" uniqKey="Pouliliou S">S Pouliliou</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Schaaf, Mb" uniqKey="Schaaf M">MB Schaaf</name>
</author>
<author>
<name sortKey="Keulers, Tg" uniqKey="Keulers T">TG Keulers</name>
</author>
<author>
<name sortKey="Vooijs, Ma" uniqKey="Vooijs M">MA Vooijs</name>
</author>
<author>
<name sortKey="Rouschop, Km" uniqKey="Rouschop K">KM Rouschop</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lai, Dh" uniqKey="Lai D">DH Lai</name>
</author>
<author>
<name sortKey="Gavin" uniqKey="Gavin">Gavin</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Fungtammasan, A" uniqKey="Fungtammasan A">A Fungtammasan</name>
</author>
<author>
<name sortKey="Walsh, E" uniqKey="Walsh E">E Walsh</name>
</author>
<author>
<name sortKey="Chiaromonte, F" uniqKey="Chiaromonte F">F Chiaromonte</name>
</author>
<author>
<name sortKey="Eckert, Ka" uniqKey="Eckert K">KA Eckert</name>
</author>
<author>
<name sortKey="Makova, Kd" uniqKey="Makova K">KD Makova</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Gyorffy, B" uniqKey="Gyorffy B">B Gyorffy</name>
</author>
<author>
<name sortKey="Lanczky, A" uniqKey="Lanczky A">A Lanczky</name>
</author>
<author>
<name sortKey="Eklund, Ac" uniqKey="Eklund A">AC Eklund</name>
</author>
<author>
<name sortKey="Denkert, C" uniqKey="Denkert C">C Denkert</name>
</author>
<author>
<name sortKey="Budczies, J" uniqKey="Budczies J">J Budczies</name>
</author>
<author>
<name sortKey="Li, Q" uniqKey="Li Q">Q Li</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Schindelin, J" uniqKey="Schindelin J">J Schindelin</name>
</author>
<author>
<name sortKey="Arganda Carreras, I" uniqKey="Arganda Carreras I">I Arganda-Carreras</name>
</author>
<author>
<name sortKey="Frise, E" uniqKey="Frise E">E Frise</name>
</author>
<author>
<name sortKey="Kaynig, V" uniqKey="Kaynig V">V Kaynig</name>
</author>
<author>
<name sortKey="Longair, M" uniqKey="Longair M">M Longair</name>
</author>
<author>
<name sortKey="Pietzsch, T" uniqKey="Pietzsch T">T Pietzsch</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ganapathy, S" uniqKey="Ganapathy S">S Ganapathy</name>
</author>
<author>
<name sortKey="Muraleedharan, A" uniqKey="Muraleedharan A">A Muraleedharan</name>
</author>
<author>
<name sortKey="Sathidevi, Ps" uniqKey="Sathidevi P">PS Sathidevi</name>
</author>
<author>
<name sortKey="Chand, P" uniqKey="Chand P">P Chand</name>
</author>
<author>
<name sortKey="Rajkumar, Rp" uniqKey="Rajkumar R">RP Rajkumar</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">PLoS Genet</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS Genet</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosgen</journal-id>
<journal-title-group>
<journal-title>PLoS Genetics</journal-title>
</journal-title-group>
<issn pub-type="ppub">1553-7390</issn>
<issn pub-type="epub">1553-7404</issn>
<publisher>
<publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, CA USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">31923184</article-id>
<article-id pub-id-type="pmc">6953790</article-id>
<article-id pub-id-type="doi">10.1371/journal.pgen.1008558</article-id>
<article-id pub-id-type="publisher-id">PGENETICS-D-18-02188</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Biology and Life Sciences</subject>
<subj-group>
<subject>Cell Biology</subject>
<subj-group>
<subject>Cell Processes</subject>
<subj-group>
<subject>Cell Death</subject>
<subj-group>
<subject>Autophagic Cell Death</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Medicine and Health Sciences</subject>
<subj-group>
<subject>Oncology</subject>
<subj-group>
<subject>Cancers and Neoplasms</subject>
<subj-group>
<subject>Gynecological Tumors</subject>
<subj-group>
<subject>Ovarian Cancer</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Research and Analysis Methods</subject>
<subj-group>
<subject>Animal Studies</subject>
<subj-group>
<subject>Experimental Organism Systems</subject>
<subj-group>
<subject>Model Organisms</subject>
<subj-group>
<subject>Mouse Models</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Research and Analysis Methods</subject>
<subj-group>
<subject>Model Organisms</subject>
<subj-group>
<subject>Mouse Models</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Research and Analysis Methods</subject>
<subj-group>
<subject>Animal Studies</subject>
<subj-group>
<subject>Experimental Organism Systems</subject>
<subj-group>
<subject>Animal Models</subject>
<subj-group>
<subject>Mouse Models</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Medicine and Health Sciences</subject>
<subj-group>
<subject>Epidemiology</subject>
<subj-group>
<subject>Medical Risk Factors</subject>
<subj-group>
<subject>Cancer Risk Factors</subject>
<subj-group>
<subject>Genetic Causes of Cancer</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Medicine and Health Sciences</subject>
<subj-group>
<subject>Oncology</subject>
<subj-group>
<subject>Cancer Risk Factors</subject>
<subj-group>
<subject>Genetic Causes of Cancer</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Biology and Life Sciences</subject>
<subj-group>
<subject>Genetics</subject>
<subj-group>
<subject>Genomics</subject>
<subj-group>
<subject>Animal Genomics</subject>
<subj-group>
<subject>Mammalian Genomics</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Biology and Life Sciences</subject>
<subj-group>
<subject>Genetics</subject>
<subj-group>
<subject>Gene Types</subject>
<subj-group>
<subject>Suppressor Genes</subject>
<subj-group>
<subject>Tumor Suppressor Genes</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Biology and Life Sciences</subject>
<subj-group>
<subject>Genetics</subject>
<subj-group>
<subject>Gene Identification and Analysis</subject>
<subj-group>
<subject>Genetic Networks</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Computer and Information Sciences</subject>
<subj-group>
<subject>Network Analysis</subject>
<subj-group>
<subject>Genetic Networks</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Biology and Life Sciences</subject>
<subj-group>
<subject>Cell Biology</subject>
<subj-group>
<subject>Chromosome Biology</subject>
<subj-group>
<subject>Chromosomes</subject>
<subj-group>
<subject>Chromosome Structure and Function</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors</article-title>
<alt-title alt-title-type="running-head">Autophagy Gene Haploinsufficiency Promotes Early Ovarian Tumors</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8978-5961</contrib-id>
<name>
<surname>Delaney</surname>
<given-names>Joe R.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Funding acquisition</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Software</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff003">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Patel</surname>
<given-names>Chandni B.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8964-1415</contrib-id>
<name>
<surname>Bapat</surname>
<given-names>Jaidev</given-names>
</name>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-0914-2967</contrib-id>
<name>
<surname>Jones</surname>
<given-names>Christian M.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ramos-Zapatero</surname>
<given-names>Maria</given-names>
</name>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-3192-4452</contrib-id>
<name>
<surname>Ortell</surname>
<given-names>Katherine K.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-1189-0777</contrib-id>
<name>
<surname>Tanios</surname>
<given-names>Ralph</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Haghighiabyaneh</surname>
<given-names>Mina</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Axelrod</surname>
<given-names>Joshua</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>DeStefano</surname>
<given-names>John W.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tancioni</surname>
<given-names>Isabelle</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schlaepfer</surname>
<given-names>David D.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8098-9888</contrib-id>
<name>
<surname>Harismendy</surname>
<given-names>Olivier</given-names>
</name>
<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff006">
<sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>La Spada</surname>
<given-names>Albert R.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff003">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stupack</surname>
<given-names>Dwayne G.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
</contrib-group>
<aff id="aff001">
<label>1</label>
<addr-line>UC San Diego Moores Cancer Center, La Jolla, California, United States of America</addr-line>
</aff>
<aff id="aff002">
<label>2</label>
<addr-line>Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</aff>
<aff id="aff003">
<label>3</label>
<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>
</aff>
<aff id="aff004">
<label>4</label>
<addr-line>Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America</addr-line>
</aff>
<aff id="aff005">
<label>5</label>
<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>
</aff>
<aff id="aff006">
<label>6</label>
<addr-line>Division of Biomedical Informatics, Department of Medicine, UC San Diego School of Medicine, La Jolla, California, United States of America</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Kwiatkowski</surname>
<given-names>David J.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">
<addr-line>Brigham and Women's Hospital, UNITED STATES</addr-line>
</aff>
<author-notes>
<fn fn-type="COI-statement" id="coi001">
<p>The authors have declared that no competing interests exist.</p>
</fn>
<corresp id="cor001">* E-mail:
<email>delaneyj@musc.edu</email>
(JRD);
<email>al.laspada@duke.edu</email>
(ARLS);
<email>dstupack@ucsd.edu</email>
(DGS)</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>10</day>
<month>1</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="collection">
<month>1</month>
<year>2020</year>
</pub-date>
<volume>16</volume>
<issue>1</issue>
<elocation-id>e1008558</elocation-id>
<history>
<date date-type="received">
<day>15</day>
<month>11</month>
<year>2018</year>
</date>
<date date-type="accepted">
<day>9</day>
<month>12</month>
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>© 2020 Delaney et al</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Delaney et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="pgen.1008558.pdf"></self-uri>
<abstract>
<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>
</abstract>
<abstract abstract-type="summary">
<title>Author summary</title>
<p>Life requires an excellent trash and recycling system. One system mammalian cells rely upon is called autophagy. Autophagy clears cells of larger forms of debris and is critical for normal cell function. We previously found that ovarian cancer cells are unable to execute normal cellular recycling during periods of stress, due to losses in core autophagy genes. Since autophagy has previously been implicated as a cancer cell survival factor, we directly investigated the impact of autophagy gene loss in ovarian cancer models. We discovered a reduction in autophagy proteins disabled normal genome quality control during cell division, leading to genomic instability. We document here for the first time whether reducing an autophagy gene in mice influences ovarian tumor formation. We found earlier ovarian tumors in autophagy deficient mice compared with control mice. We conclude that serous ovarian carcinomas, which rank among the most genetically altered cancers, gain their hallmark genomic instability in part by losing autophagy genes.</p>
</abstract>
<funding-group>
<award-group id="award001">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000054</institution-id>
<institution>National Cancer Institute</institution>
</institution-wrap>
</funding-source>
<award-id>CA207729</award-id>
<principal-award-recipient>
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8978-5961</contrib-id>
<name>
<surname>Delaney</surname>
<given-names>Joe R.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award002">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>CA107263</award-id>
<principal-award-recipient>
<name>
<surname>Stupack</surname>
<given-names>Dwayne G.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award003">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>CA102310</award-id>
<principal-award-recipient>
<name>
<surname>Schlaepfer</surname>
<given-names>David D.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award004">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>CA177519</award-id>
<principal-award-recipient>
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8098-9888</contrib-id>
<name>
<surname>Harismendy</surname>
<given-names>Olivier</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award005">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>AG033082</award-id>
<principal-award-recipient>
<name>
<surname>La Spada</surname>
<given-names>Albert R.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award006">
<funding-source>
<institution>Nine Girls Ask</institution>
</funding-source>
<principal-award-recipient>
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8978-5961</contrib-id>
<name>
<surname>Delaney</surname>
<given-names>Joe R.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award007">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>CA138313</award-id>
</award-group>
<award-group id="award008">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>DK063491</award-id>
</award-group>
<award-group id="award009">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>CA023100</award-id>
</award-group>
<award-group id="award010">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>GM132055</award-id>
<principal-award-recipient>
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-0914-2967</contrib-id>
<name>
<surname>Jones</surname>
<given-names>Christian M.</given-names>
</name>
</principal-award-recipient>
</award-group>
<funding-statement>This work was supported by NIH grants CA207729 (JD), GM132055 (CJ), CA107263 (DGS), CA177519 (OH), CA102310 (DS), AG033082 (ALS), and by funding from the non-profit Nine Girls Ask Foundation (
<ext-link ext-link-type="uri" xlink:href="https://www.ninegirlsask.com/">https://www.ninegirlsask.com/</ext-link>
) (DGS, DS, JD). Supported in part by pilot research funding, Hollings Cancer Center’s Cancer Center Support Grant P30 CA138313 at the Medical University of South Carolina. Supported in part by the Statistics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (P30 CA138313). Sequencing at the IGM was supported by NIH grants P30DK063491 and P30CA023100. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts>
<fig-count count="6"></fig-count>
<table-count count="0"></table-count>
<page-count count="28"></page-count>
</counts>
<custom-meta-group>
<custom-meta id="data-availability">
<meta-name>Data Availability</meta-name>
<meta-value>In additional to the processed supplemental data, raw CEL files used to determine SKOV3 CNAs are available in the GEO repository GSE122433. Raw FASTQ files used to determine murine CNAs are deposited in the Sequence Read Archive (SRA) under accession number PRJNA505181.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes>
<title>Data Availability</title>
<p>In additional to the processed supplemental data, raw CEL files used to determine SKOV3 CNAs are available in the GEO repository GSE122433. Raw FASTQ files used to determine murine CNAs are deposited in the Sequence Read Archive (SRA) under accession number PRJNA505181.</p>
</notes>
</front>
</pmc>
<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>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Pmc/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000192 | SxmlIndent | more

Ou

HfdSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd -nk 000192 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    ChloroquineV1
   |flux=    Pmc
   |étape=   Checkpoint
   |type=    RBID
   |clé=     PMC:6953790
   |texte=   Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i   -Sk "pubmed:31923184" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd   \
       | NlmPubMed2Wicri -a ChloroquineV1 

Wicri

This area was generated with Dilib version V0.6.33.
Data generation: Wed Mar 25 22:43:59 2020. Site generation: Sun Jan 31 12:44:45 2021