title: Vertical Magnetic Separation of Circulating Tumor Cells for Somatic Genomic-Alteration Analysis in Lung Cancer Patients.
abstract: Efficient isolation and genetic analysis of circulating tumor cells (CTCs) from cancer patients' blood is a critical step for clinical applications using CTCs. Here, we report a novel CTC-isolation method and subsequent genetic analysis. CTCs from the blood were complexed with magnetic beads coated with antibodies against the epithelial cell adhesion molecule (EpCAM) and separated vertically on a density-gradient medium in a modified well-plate. The recovery rate of model CTCs was reasonable and the cell purity was enhanced dramatically when compared to those parameters obtained using a conventional magnetic isolation method. CTCs were recovered from an increased number of patient samples using our magnetic system vs. the FDA-approved CellSearch system (100% vs. 33%, respectively). In 8 of 13 cases, targeted deep sequencing analysis of CTCs revealed private point mutations present in CTCs but not in matched tumor samples and white blood cells (WBCs), which was also validated by droplet digital PCR. Copy-number alterations in CTCs were also observed in the corresponding tumor tissues for some patients. In this report, we showed that CTCs isolated by the EpCAM-based method had complex and diverse genetic features that were similar to those of tumor samples in some, but not all, cases.
authors.affiliation: Samsung Biomedical Research Institute (SBRI), Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Seoul 06351, Korea.|Samsung Genome Institute (SGI), Samsung Medical Center (SMC), Seoul 06351, Korea.
authors.forename: Chang Eun
authors.initials: CE
authors.lastname: Yoo
authors.affiliation: Samsung Electronics Co. Ltd., Suwon, 16677, Korea.
authors.forename: Jong-Myeon
authors.initials: JM
authors.lastname: Park
authors.affiliation: Samsung Biomedical Research Institute (SBRI), Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Seoul 06351, Korea.|Samsung Genome Institute (SGI), Samsung Medical Center (SMC), Seoul 06351, Korea.
authors.forename: Hui-Sung
authors.initials: HS
authors.lastname: Moon
authors.affiliation: Samsung Genome Institute (SGI), Samsung Medical Center (SMC), Seoul 06351, Korea.
authors.forename: Je-Gun
authors.initials: JG
authors.lastname: Joung
authors.affiliation: Samsung Biomedical Research Institute (SBRI), Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Seoul 06351, Korea.|Samsung Genome Institute (SGI), Samsung Medical Center (SMC), Seoul 06351, Korea.
authors.forename: Dae-Soon
authors.initials: DS
authors.lastname: Son
authors.affiliation: Samsung Genome Institute (SGI), Samsung Medical Center (SMC), Seoul 06351, Korea.
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Jeon
authors.affiliation: Samsung Biomedical Research Institute (SBRI), Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Seoul 06351, Korea.|Samsung Genome Institute (SGI), Samsung Medical Center (SMC), Seoul 06351, Korea.
authors.forename: Yeon Jeong
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Samsung Biomedical Research Institute (SBRI), Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Seoul 06351, Korea.|Samsung Genome Institute (SGI), Samsung Medical Center (SMC), Seoul 06351, Korea.
authors.forename: Kyung-Yeon
authors.initials: KY
authors.lastname: Han
authors.affiliation: Department of Medicine, Sungkyunkwan University School of Medicine, Suwon 16416, Korea.
authors.forename: Jong-Mu
authors.initials: JM
authors.lastname: Sun
authors.affiliation: Department of Medicine, Sungkyunkwan University School of Medicine, Suwon 16416, Korea.
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.affiliation: Samsung Biomedical Research Institute (SBRI), Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Seoul 06351, Korea.|Samsung Genome Institute (SGI), Samsung Medical Center (SMC), Seoul 06351, Korea.
authors.forename: Donghyun
authors.initials: D
authors.lastname: Park
authors.affiliation: Samsung Genome Institute (SGI), Samsung Medical Center (SMC), Seoul 06351, Korea.|Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
mesh_terms: D000483:Alleles; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D056915:DNA Copy Number Variations; D000071858:Epithelial Cell Adhesion Molecule / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005787:Gene Frequency; D006801:Humans; D018189:Immunomagnetic Separation / Q000295:instrumentation / Q000379:methods*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D017354:Point Mutation; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D009363:Neoplasm Proteins