Detection of Cancer DNA in Plasma of Patients with Early-Stage Breast Cancer
Identifieur interne : 003C29 ( PascalFrancis/Curation ); précédent : 003C28; suivant : 003C30Detection 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
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
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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<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="01"><s1>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</s1>
<s2>Baltimore, Maryland</s2>
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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="1"><inist:fA14 i1="01"><s1>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</s1>
<s2>Baltimore, Maryland</s2>
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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="1"><inist:fA14 i1="04"><s1>RainDance Technologies</s1>
<s2>Billerica, Massachusetts</s2>
<s3>USA</s3>
<sZ>23 aut.</sZ>
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</affiliation>
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<author><name sortKey="Maar, Dianna" sort="Maar, Dianna" uniqKey="Maar D" first="Dianna" last="Maar">Dianna Maar</name>
<affiliation wicri:level="1"><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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</affiliation>
</author>
<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>
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<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>Biological fluid</term>
<term>Blood plasma</term>
<term>Breast cancer</term>
<term>DNA</term>
<term>Detection</term>
<term>Diagnosis</term>
<term>Early stage</term>
<term>Human</term>
<term>Malignant tumor</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Détection</term>
<term>Diagnostic</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>
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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>
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