Oncotarget

Clinical Research Papers:

Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform

Evelyn Kidess, Kyra Heirich, Matthew Wiggin, Valentina Vysotskaia, Brendan C. Visser, Andre Marziali, Bertram Wiedenmann, Jeffrey A. Norton, Mark Lee, Stefanie S. Jeffrey and George A. Poultsides _

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Oncotarget. 2015; 6:2549-2561. https://doi.org/10.18632/oncotarget.3041

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Abstract

Evelyn Kidess1, Kyra Heirich1, Matthew Wiggin2, Valentina Vysotskaia2, Brendan C. Visser1, Andre Marziali2, Bertram Wiedenmann3, Jeffrey A. Norton1, Mark Lee2, Stefanie S. Jeffrey1 and George A. Poultsides1

1 Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA

2 Boreal Genomics, Mountain View, CA, USA and Vancouver, BC, Canada

3 Deparment of Medicine, Division of Hepatology and Gastroenterology, Charité University Hospital, Berlin, Germany

Correspondence:

Stefanie S. Jeffrey, email:

George A. Poultsides, email:

Keywords: biomarker, circulating tumor DNA, colon cancer, ctDNA, hepatic metastasis

Received: September 04, 2014 Accepted: December 09, 2014 Published: December 10, 2014

Abstract

BACKROUND: Circulating tumor DNA (ctDNA) holds promise as a non-invasive means for tumor monitoring in solid malignancies. Assays with high sensitivity and multiplexed analysis of mutations are needed to enable broad application.

METHODS: We developed a new assay based on sequence-specific synchronous coefficient of drag alteration (SCODA) technology, which enriches for mutant DNA to achieve high sensitivity and specificity. This assay was applied to plasma and tumor tissue from non-metastatic and metastatic colorectal cancer (CRC) patients, including patients undergoing surgical resection for CRC liver metastases.

RESULTS: Across multiple characterization experiments, the assay demonstrated a limit of detection of 0.001% (1 molecule in 100,000) for the majority of the 46 mutations in the panel. In CRC patient samples (n=38), detected mutations were concordant in tissue and plasma for 93% of metastatic patients versus 54% of non-metastatic patients. For three patients, ctDNA identified additional mutations not detected in tumor tissue. In patients undergoing liver metastatectomy, ctDNA anticipated tumor recurrence earlier than carcinoembryonic antigen (CEA) value or imaging.

CONCLUSIONS: The multiplexed SCODA mutation enrichment and detection method can be applied to mutation profiling and quantitation of ctDNA, and is likely to have particular utility in the metastatic setting, including patients undergoing metastatectomy.


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