Detection of Cancer DNA in Plasma of Patients with Early-Stage Breast Cancer
Identifieur interne : 005662 ( Main/Exploration ); précédent : 005661; suivant : 005663Detection of Cancer DNA in Plasma of Patients with Early-Stage Breast Cancer
Auteurs : Julia A. Beaver [États-Unis] ; Danijela Jelovac [États-Unis] ; Sasidharan Balukrishna [Inde] ; Rory L. Cochran [États-Unis] ; Sarah Croessmann [États-Unis] ; Daniel J. Zabransky [États-Unis] ; HONG YUEN WONG [États-Unis] ; Patricia Valda Toro [États-Unis] ; Justin Cidado [États-Unis] ; Brian G. Blair [États-Unis] ; David Chu [États-Unis] ; Timothy Burns [États-Unis] ; Michaela J. Higgins [États-Unis] ; Vered Stearns [États-Unis] ; Lisa Jacobs [États-Unis] ; Mehran Habibi [États-Unis] ; Julie Lange [États-Unis] ; Paula J. Hurley [États-Unis] ; Josh Lauring [États-Unis] ; Dustin A. Vandenberg [États-Unis] ; Jill Kessler [États-Unis] ; Stacie Jeter [États-Unis] ; Michael L. Samuels [États-Unis] ; Dianna Maar [États-Unis] ; Leslie Cope ; Ashley Cimino-Mathews ; Pedram Argani ; Antonio C. Wolff ; BEN HO PARKSource :
- Clinical cancer research : (Print) [ 1078-0432 ] ; 2014.
Descripteurs français
- KwdFr :
- ADN tumoral (), ADN tumoral (génétique), ADN tumoral (sang), Adulte, Adulte d'âge moyen, Analyse de mutations d'ADN (), Exons (génétique), Femelle, Humains, Mutation, Phosphatidylinositol 3-kinases (génétique), Période postopératoire, Période préopératoire, Reproductibilité des résultats, Réaction de polymérisation en chaîne (), Sensibilité et spécificité, Stade de la tumeur, Sujet âgé, Tumeurs du sein (), Tumeurs du sein (diagnostic), Tumeurs du sein (génétique), Études prospectives.
- MESH :
- diagnostic : Tumeurs du sein.
- génétique : ADN tumoral, Exons, Phosphatidylinositol 3-kinases, Tumeurs du sein.
- sang : ADN tumoral.
- Pascal (Inist)
- ADN tumoral, Adulte, Adulte d'âge moyen, Analyse de mutations d'ADN, Détection, Diagnostic, Femelle, Humains, Mutation, Période postopératoire, Période préopératoire, Reproductibilité des résultats, Réaction de polymérisation en chaîne, Sensibilité et spécificité, Stade de la tumeur, Sujet âgé, Tumeur maligne, Cancer du sein, DNA, Liquide biologique, Plasma sanguin, Homme, Stade précoce, Tumeurs du sein, Études prospectives.
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Adult, Aged, Biological fluid, Blood plasma, Breast Neoplasms (diagnosis), Breast Neoplasms (genetics), Breast Neoplasms (surgery), Breast cancer, DNA, DNA Mutational Analysis (methods), DNA, Neoplasm (blood), DNA, Neoplasm (chemistry), DNA, Neoplasm (genetics), Detection, Diagnosis, Early stage, Exons (genetics), Female, Human, Humans, Malignant tumor, Middle Aged, Mutation, Neoplasm Staging, Phosphatidylinositol 3-Kinases (genetics), Polymerase Chain Reaction (methods), Postoperative Period, Preoperative Period, Prospective Studies, Reproducibility of Results, Sensitivity and Specificity.
- MESH :
- chemical , blood : DNA, Neoplasm.
- chemical , chemistry : DNA, Neoplasm.
- diagnosis : Breast Neoplasms.
- genetics : Breast Neoplasms, DNA, Neoplasm, Exons, Phosphatidylinositol 3-Kinases.
- methods : DNA Mutational Analysis, Polymerase Chain Reaction.
- surgery : Breast Neoplasms.
- Adult, Aged, Female, Humans, Middle Aged, Mutation, Neoplasm Staging, Postoperative Period, Preoperative Period, Prospective Studies, Reproducibility of Results, Sensitivity and Specificity.
Abstract
Purpose: Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection. Experimental Design: In this prospective study, primary breast tumors and matched pre- and postsurgery blood samples were collected from patients with early-stage breast cancer (n = 29). Tumors (n = 30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR. Results: Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Presurgery plasma samples (n = 29) were then analyzed for PIK3CA mutations using ddPCR. Of the 15 PIK3CA mutations detected in tumors by ddPCR, 14 of the corresponding mutations were detected in presurgical ptDNA, whereas no mutations were found in plasma from patients with PIK3CA wild-type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation-positive ptDNA presurgery had ddPCR analysis of postsurgery plasma, with five patients having detectable ptDNA postsurgery. Conclusions: This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in patients with early-stage breast cancer. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients.
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Le document en format XML
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<author><name sortKey="Stearns, Vered" sort="Stearns, Vered" uniqKey="Stearns V" first="Vered" last="Stearns">Vered Stearns</name>
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<author><name sortKey="Jacobs, Lisa" sort="Jacobs, Lisa" uniqKey="Jacobs L" first="Lisa" last="Jacobs">Lisa Jacobs</name>
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<author><name sortKey="Habibi, Mehran" sort="Habibi, Mehran" uniqKey="Habibi M" first="Mehran" last="Habibi">Mehran Habibi</name>
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<author><name sortKey="Lange, Julie" sort="Lange, Julie" uniqKey="Lange J" first="Julie" last="Lange">Julie Lange</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Detection of Cancer DNA in Plasma of Patients with Early-Stage Breast Cancer</title>
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<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Christian Medical College Vellore</s1>
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<country>Inde</country>
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<author><name sortKey="Zabransky, Daniel J" sort="Zabransky, Daniel J" uniqKey="Zabransky D" first="Daniel J." last="Zabransky">Daniel J. Zabransky</name>
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<author><name sortKey="Hong Yuen Wong" sort="Hong Yuen Wong" uniqKey="Hong Yuen Wong" last="Hong Yuen Wong">HONG YUEN WONG</name>
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<author><name sortKey="Blair, Brian G" sort="Blair, Brian G" uniqKey="Blair B" first="Brian G." last="Blair">Brian G. Blair</name>
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<author><name sortKey="Stearns, Vered" sort="Stearns, Vered" uniqKey="Stearns V" first="Vered" last="Stearns">Vered Stearns</name>
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<author><name sortKey="Jacobs, Lisa" sort="Jacobs, Lisa" uniqKey="Jacobs L" first="Lisa" last="Jacobs">Lisa Jacobs</name>
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<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</s1>
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<author><name sortKey="Lauring, Josh" sort="Lauring, Josh" uniqKey="Lauring J" first="Josh" last="Lauring">Josh Lauring</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</s1>
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<author><name sortKey="Vandenberg, Dustin A" sort="Vandenberg, Dustin A" uniqKey="Vandenberg D" first="Dustin A." last="Vandenberg">Dustin A. Vandenberg</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</s1>
<s2>Baltimore, Maryland</s2>
<s3>USA</s3>
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<author><name sortKey="Kessler, Jill" sort="Kessler, Jill" uniqKey="Kessler J" first="Jill" last="Kessler">Jill Kessler</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</s1>
<s2>Baltimore, Maryland</s2>
<s3>USA</s3>
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<author><name sortKey="Jeter, Stacie" sort="Jeter, Stacie" uniqKey="Jeter S" first="Stacie" last="Jeter">Stacie Jeter</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</s1>
<s2>Baltimore, Maryland</s2>
<s3>USA</s3>
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<author><name sortKey="Samuels, Michael L" sort="Samuels, Michael L" uniqKey="Samuels M" first="Michael L." last="Samuels">Michael L. Samuels</name>
<affiliation wicri:level="2"><inist:fA14 i1="04"><s1>RainDance Technologies</s1>
<s2>Billerica, Massachusetts</s2>
<s3>USA</s3>
<sZ>23 aut.</sZ>
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<country>États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
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</author>
<author><name sortKey="Maar, Dianna" sort="Maar, Dianna" uniqKey="Maar D" first="Dianna" last="Maar">Dianna Maar</name>
<affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Bio-Rad Laboratories, Digital Biology Center</s1>
<s2>Pleasanton, California</s2>
<s3>USA</s3>
<sZ>24 aut.</sZ>
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<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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<author><name sortKey="Cope, Leslie" sort="Cope, Leslie" uniqKey="Cope L" first="Leslie" last="Cope">Leslie Cope</name>
</author>
<author><name sortKey="Cimino Mathews, Ashley" sort="Cimino Mathews, Ashley" uniqKey="Cimino Mathews A" first="Ashley" last="Cimino-Mathews">Ashley Cimino-Mathews</name>
</author>
<author><name sortKey="Argani, Pedram" sort="Argani, Pedram" uniqKey="Argani P" first="Pedram" last="Argani">Pedram Argani</name>
</author>
<author><name sortKey="Wolff, Antonio C" sort="Wolff, Antonio C" uniqKey="Wolff A" first="Antonio C." last="Wolff">Antonio C. Wolff</name>
</author>
<author><name sortKey="Ben Ho Park" sort="Ben Ho Park" uniqKey="Ben Ho Park" last="Ben Ho Park">BEN HO PARK</name>
</author>
</analytic>
<series><title level="j" type="main">Clinical cancer research : (Print)</title>
<title level="j" type="abbreviated">Clin. cancer res. : (Print)</title>
<idno type="ISSN">1078-0432</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Clinical cancer research : (Print)</title>
<title level="j" type="abbreviated">Clin. cancer res. : (Print)</title>
<idno type="ISSN">1078-0432</idno>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Biological fluid</term>
<term>Blood plasma</term>
<term>Breast Neoplasms (diagnosis)</term>
<term>Breast Neoplasms (genetics)</term>
<term>Breast Neoplasms (surgery)</term>
<term>Breast cancer</term>
<term>DNA</term>
<term>DNA Mutational Analysis (methods)</term>
<term>DNA, Neoplasm (blood)</term>
<term>DNA, Neoplasm (chemistry)</term>
<term>DNA, Neoplasm (genetics)</term>
<term>Detection</term>
<term>Diagnosis</term>
<term>Early stage</term>
<term>Exons (genetics)</term>
<term>Female</term>
<term>Human</term>
<term>Humans</term>
<term>Malignant tumor</term>
<term>Middle Aged</term>
<term>Mutation</term>
<term>Neoplasm Staging</term>
<term>Phosphatidylinositol 3-Kinases (genetics)</term>
<term>Polymerase Chain Reaction (methods)</term>
<term>Postoperative Period</term>
<term>Preoperative Period</term>
<term>Prospective Studies</term>
<term>Reproducibility of Results</term>
<term>Sensitivity and Specificity</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ADN tumoral ()</term>
<term>ADN tumoral (génétique)</term>
<term>ADN tumoral (sang)</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de mutations d'ADN ()</term>
<term>Exons (génétique)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mutation</term>
<term>Phosphatidylinositol 3-kinases (génétique)</term>
<term>Période postopératoire</term>
<term>Période préopératoire</term>
<term>Reproductibilité des résultats</term>
<term>Réaction de polymérisation en chaîne ()</term>
<term>Sensibilité et spécificité</term>
<term>Stade de la tumeur</term>
<term>Sujet âgé</term>
<term>Tumeurs du sein ()</term>
<term>Tumeurs du sein (diagnostic)</term>
<term>Tumeurs du sein (génétique)</term>
<term>Études prospectives</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>DNA, Neoplasm</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>DNA, Neoplasm</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Breast Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Tumeurs du sein</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Breast Neoplasms</term>
<term>DNA, Neoplasm</term>
<term>Exons</term>
<term>Phosphatidylinositol 3-Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN tumoral</term>
<term>Exons</term>
<term>Phosphatidylinositol 3-kinases</term>
<term>Tumeurs du sein</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>DNA Mutational Analysis</term>
<term>Polymerase Chain Reaction</term>
</keywords>
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</keywords>
<keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Breast Neoplasms</term>
</keywords>
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<term>Aged</term>
<term>Female</term>
<term>Humans</term>
<term>Middle Aged</term>
<term>Mutation</term>
<term>Neoplasm Staging</term>
<term>Postoperative Period</term>
<term>Preoperative Period</term>
<term>Prospective Studies</term>
<term>Reproducibility of Results</term>
<term>Sensitivity and Specificity</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>ADN tumoral</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de mutations d'ADN</term>
<term>Détection</term>
<term>Diagnostic</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mutation</term>
<term>Période postopératoire</term>
<term>Période préopératoire</term>
<term>Reproductibilité des résultats</term>
<term>Réaction de polymérisation en chaîne</term>
<term>Sensibilité et spécificité</term>
<term>Stade de la tumeur</term>
<term>Sujet âgé</term>
<term>Tumeur maligne</term>
<term>Cancer du sein</term>
<term>DNA</term>
<term>Liquide biologique</term>
<term>Plasma sanguin</term>
<term>Homme</term>
<term>Stade précoce</term>
<term>Tumeurs du sein</term>
<term>Études prospectives</term>
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<front><div type="abstract" xml:lang="en">Purpose: Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection. Experimental Design: In this prospective study, primary breast tumors and matched pre- and postsurgery blood samples were collected from patients with early-stage breast cancer (n = 29). Tumors (n = 30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR. Results: Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Presurgery plasma samples (n = 29) were then analyzed for PIK3CA mutations using ddPCR. Of the 15 PIK3CA mutations detected in tumors by ddPCR, 14 of the corresponding mutations were detected in presurgical ptDNA, whereas no mutations were found in plasma from patients with PIK3CA wild-type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation-positive ptDNA presurgery had ddPCR analysis of postsurgery plasma, with five patients having detectable ptDNA postsurgery. Conclusions: This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in patients with early-stage breast cancer. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients.</div>
</front>
</TEI>
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<li>États-Unis</li>
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<name sortKey="Cope, Leslie" sort="Cope, Leslie" uniqKey="Cope L" first="Leslie" last="Cope">Leslie Cope</name>
<name sortKey="Wolff, Antonio C" sort="Wolff, Antonio C" uniqKey="Wolff A" first="Antonio C." last="Wolff">Antonio C. Wolff</name>
</noCountry>
<country name="États-Unis"><region name="Maryland"><name sortKey="Beaver, Julia A" sort="Beaver, Julia A" uniqKey="Beaver J" first="Julia A." last="Beaver">Julia A. Beaver</name>
</region>
<name sortKey="Blair, Brian G" sort="Blair, Brian G" uniqKey="Blair B" first="Brian G." last="Blair">Brian G. Blair</name>
<name sortKey="Burns, Timothy" sort="Burns, Timothy" uniqKey="Burns T" first="Timothy" last="Burns">Timothy Burns</name>
<name sortKey="Chu, David" sort="Chu, David" uniqKey="Chu D" first="David" last="Chu">David Chu</name>
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<name sortKey="Cochran, Rory L" sort="Cochran, Rory L" uniqKey="Cochran R" first="Rory L." last="Cochran">Rory L. Cochran</name>
<name sortKey="Croessmann, Sarah" sort="Croessmann, Sarah" uniqKey="Croessmann S" first="Sarah" last="Croessmann">Sarah Croessmann</name>
<name sortKey="Habibi, Mehran" sort="Habibi, Mehran" uniqKey="Habibi M" first="Mehran" last="Habibi">Mehran Habibi</name>
<name sortKey="Higgins, Michaela J" sort="Higgins, Michaela J" uniqKey="Higgins M" first="Michaela J." last="Higgins">Michaela J. Higgins</name>
<name sortKey="Hong Yuen Wong" sort="Hong Yuen Wong" uniqKey="Hong Yuen Wong" last="Hong Yuen Wong">HONG YUEN WONG</name>
<name sortKey="Hurley, Paula J" sort="Hurley, Paula J" uniqKey="Hurley P" first="Paula J." last="Hurley">Paula J. Hurley</name>
<name sortKey="Jacobs, Lisa" sort="Jacobs, Lisa" uniqKey="Jacobs L" first="Lisa" last="Jacobs">Lisa Jacobs</name>
<name sortKey="Jelovac, Danijela" sort="Jelovac, Danijela" uniqKey="Jelovac D" first="Danijela" last="Jelovac">Danijela Jelovac</name>
<name sortKey="Jeter, Stacie" sort="Jeter, Stacie" uniqKey="Jeter S" first="Stacie" last="Jeter">Stacie Jeter</name>
<name sortKey="Kessler, Jill" sort="Kessler, Jill" uniqKey="Kessler J" first="Jill" last="Kessler">Jill Kessler</name>
<name sortKey="Lange, Julie" sort="Lange, Julie" uniqKey="Lange J" first="Julie" last="Lange">Julie Lange</name>
<name sortKey="Lauring, Josh" sort="Lauring, Josh" uniqKey="Lauring J" first="Josh" last="Lauring">Josh Lauring</name>
<name sortKey="Maar, Dianna" sort="Maar, Dianna" uniqKey="Maar D" first="Dianna" last="Maar">Dianna Maar</name>
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