title: Development of a Novel c-MET-Based CTC Detection Platform.
abstract: Amplification of the MET oncogene is associated with poor prognosis, metastatic dissemination, and drug resistance in many malignancies. We developed a method to capture and characterize circulating tumor cells (CTC) expressing c-MET using a ferromagnetic antibody. Immunofluorescence was used to characterize cells for c-MET, DAPI, and pan-CK, excluding CD45(+) leukocytes. The assay was validated using appropriate cell line controls spiked into peripheral blood collected from healthy volunteers (HV). In addition, peripheral blood was analyzed from patients with metastatic gastric, pancreatic, colorectal, bladder, renal, or prostate cancers. CTCs captured by c-MET were enumerated, and DNA FISH for MET amplification was performed. The approach was highly sensitive (80%) for MET-amplified cells, sensitive (40%-80%) for c-MET-overexpressed cells, and specific (100%) for both c-MET-negative cells and in 20 HVs. Of 52 patients with metastatic carcinomas tested, c-MET CTCs were captured in replicate samples from 3 patients [gastric, colorectal, and renal cell carcinoma (RCC)] with 6% prevalence. CTC FISH demonstrated that MET amplification in both gastric and colorectal cancer patients and trisomy 7 with gain of MET gene copies in the RCC patient. The c-MET CTC assay is a rapid, noninvasive, sensitive, and specific method for detecting MET-amplified tumor cells. CTCs with MET amplification can be detected in patients with gastric, colorectal, and renal cancers.
  
  
  
  This study developed a novel c-MET CTC assay for detecting c-MET CTCs in patients with MET amplification and warrants further investigation to determine its clinical applicability. Mol Cancer Res; 14(6); 539-47. ©2016 AACR.
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Rengasamy
authors.initials: R
authors.lastname: Boominathan
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Brad
authors.initials: B
authors.lastname: Foulk
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Chandra
authors.initials: C
authors.lastname: Rao
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Gabor
authors.initials: G
authors.lastname: Kemeny
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: John H
authors.initials: JH
authors.lastname: Strickler
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Harrison
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: David S
authors.initials: DS
authors.lastname: Hsu
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Patrick
authors.initials: P
authors.lastname: Healy
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Cinthia
authors.initials: C
authors.lastname: Pi
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Prendergast
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Carey
authors.initials: C
authors.lastname: Hobbs
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gemberling
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Mark
authors.initials: M
authors.lastname: Connelly
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
authors.forename: Mariano A
authors.initials: MA
authors.lastname: Garcia-Blanco
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina. Department of Pharmacology and Cancer Biology, Duke University, Durham, NC. andrew.armstrong@duke.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
mesh_terms: D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D005240:Feasibility Studies; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D010865:Pilot Projects; D011446:Prospective Studies; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met