Detection of PIK3CA Mutations in Plasma Tumor DNA Circulating in Peripheral Blood of Breast Cancer Patients

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dc.contributor.committeeMemberPark, Ben H.en_US
dc.contributor.committeeMemberHorner, Robert D.en_US
dc.creatorValda Toro, Patricia Lourdesen_US
dc.date.accessioned2014-12-23T05:18:43Z
dc.date.available2014-12-23T05:18:43Z
dc.date.created2014-05en_US
dc.date.issued2014-04-10en_US
dc.date.submittedMay 2014en_US
dc.description.abstractTumor-specific mutations are used as genetic biomarkers for breast cancer diagnosis and prognosis. The detection and quantification of mutations in tumor DNA circulating in peripheral blood offers a non-invasive approach for measuring the presence of cancer in patients and for evaluating individual responses to targeted therapies. We studied the feasibility of detecting two common mutations in the phosphatidylinositol- 4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene, in circulating plasma tumor DNA (ptDNA) of early stage breast cancer patients. We used two Polymerase Chain Reaction platforms, BEAMing and droplet digital PCR (ddPCR), and showed that both platforms detect PIK3CA mutations in ptDNA with high specificity and differential sensitivity (30% for BEAMing, and 93.3% for ddPCR). Additionally, we showed that the sensitivity of ddPCR for ptDNA detection decreased in blood stored at room temperature for one week in tubes that do not prevent blood lysis. Our results provide a novel and non-invasive alternative for clinically detecting and quantifying breast cancer biomarkers in blood, and suggest the use of blood collection tubes that prevent lymphocyte lysis for blood storage and transportation. The method presented herein, can allow physicians to measure tumor burden in breast cancer patients in response to targeted therapies, and to make more informed decisions regarding the administration of toxic systemic therapies.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.urihttp://jhir.library.jhu.edu/handle/1774.2/37105
dc.languageen
dc.publisherJohns Hopkins University
dc.subjectbreast canceren_US
dc.subjectearly stage breast canceren_US
dc.subjectPIK3CA mutationsen_US
dc.subjectcell-free DNAen_US
dc.subjectplasma tumor DNAen_US
dc.subjectcancer biomarkersen_US
dc.subjectcancer therapiesen_US
dc.subjectcancer geneticsen_US
dc.subjectdroplet digital PCRen_US
dc.titleDetection of PIK3CA Mutations in Plasma Tumor DNA Circulating in Peripheral Blood of Breast Cancer Patientsen_US
dc.typeThesisen_US
dc.type.materialtexten_US
thesis.degree.departmentBiochemistry, Cellular and Molecular Biologyen_US
thesis.degree.disciplineHuman Genetics and Molecular Biologyen_US
thesis.degree.grantorJohns Hopkins Universityen_US
thesis.degree.grantorKrieger School of Arts and Sciencesen_US
thesis.degree.levelMastersen_US
thesis.degree.nameM.S.en_US
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