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Elizabeth L. et al. (2017) DOI: 10.1200/JCO.2016.70.4627 
30 plasma (blood) and tumor samples obtained
Group I: Patients w...
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Medical diagnostics

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Medical diagnostics

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Medical diagnostics

  1. 1. Elizabeth L. et al. (2017) DOI: 10.1200/JCO.2016.70.4627  30 plasma (blood) and tumor samples obtained Group I: Patients with history of malignancy before diagnosis of HGSC Group II: Patients with recurrent HGSC - performed using primers flanking BRCA1/2 mutations - primer design not based on prior knowledge of reversion sequences - reversions analyzed in both tumor and plasma samples - results subsequently matched to understand significance of cf-DNA liquid biopsy in identifying BRCA1/2 mutations and reversions - BRCA1/2 mutations found in all analyzed tumor samples - reversions found in only 4 tumor samples from group II Targeted Amplicon Sequencing Chemotherapy with platins and poly-ADP ribose polymerase inhibitor-based drugs is ineffective in patients with BRCA1/2 reversion mutations Liquid Biopsy Targeted Amplicon Sequencing Patients with BRCA1/2 reversions in tumor samples Positive predictive value = 1 Negative predictive value = 0.9 PatientswithBRCA1/2 reversionsinplasmasamples Positive Positive Negative Negative True positive False positive True negativeFalse negative 4 0 242 Patients with BCRA1/2 reversions Emergence of drug resistance and relapse Chemotherapy Reversion of BRCA1/2 Germline Mutations Detected in Circulating Tumor DNA From Patients With High-Grade Serous Ovarian Cancer Predicting Therapeutic Outcome in High-Grade Serous Ovarian Cancer by Circulating DNA Analysis Chemotherapy response in patients with HGSC can be predicted using a noninvasive liquid biopsy - mutations favor response to chemtherapy - reversions could result in chemoresistance Cell-Free DNA (cf-DNA) - freely circulating molecules in blood - contain DNA of tumor origin Liquid Biopsy - can analyze BRCA1/2 mutations in cf-DNA samples - can predict treatment outcome if successful BRCA1/2 mutations & reversions 30 patients with HGSC with BRCA1/2 mutations HGSC = High-Grade Serous Ovarian Cancer Background Methodology Results Outcome www.ascopubs.org/journal/jco/  | /ASCOCancer  | @ASCO   

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