Development of a Novel c-MET-Based CTC Detection Platform.
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UNLABELLED: 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. 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.
Published Version (Please cite this version)10.1158/1541-7786.MCR-16-0011
Publication InfoAbbruzzese, J; Armstrong, AJ; Boominathan, R; Connelly, MA; Foulk, B; Garcia-Blanco, Mariano Agustin; ... Zhang, T (2016). Development of a Novel c-MET-Based CTC Detection Platform. Mol Cancer Res, 14(6). pp. 539-547. 10.1158/1541-7786.MCR-16-0011. Retrieved from http://hdl.handle.net/10161/11944.
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D. C. I. Professor of Medical Oncology
My research interests include the clinical study and treatment of pancreatic cancer.
Adjunct Professor in the Molecular Genetics and Microbiology
Human and viral genes are complex genetic units of information that are tightly regulated. The laboratory studies three aspects of this regulation: the interface between synthesis of mammalian messenger RNAs and the processing events required to mature these transcripts, the alternative processing of these messenger RNAs to produce multiple proteins from one gene, and the regulation of gene expression in human pathogenic flaviviruses. In the great majority of human transcripts
Professor of Medicine
Associate Professor of Dermatology
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