Development of a Novel c-MET–Based CTC Detection Platform

  • Tian Zhang
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Rengasamy Boominathan
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Brad Foulk
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Chandra Rao
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Gabor Kemeny
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • John H. Strickler
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • James L. Abbruzzese
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Michael R. Harrison
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • David S. Hsu
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Patrick Healy
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Jing Li
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Cinthia Pi
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Katherine M. Prendergast
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Carey Hobbs
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Sarah Gemberling
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Daniel J. George
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Herbert I. Hurwitz
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Mark Connelly
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Mariano A. Garcia-Blanco
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.
  • Andrew J. Armstrong
    1Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina.

抄録

<jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>Implications: 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.</jats:p>

収録刊行物

  • Molecular Cancer Research

    Molecular Cancer Research 14 (6), 539-547, 2016-06-01

    American Association for Cancer Research (AACR)

被引用文献 (1)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ