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

dc.contributor.author

Zhang, Tian

dc.contributor.author

Boominathan, Rengasamy

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Foulk, Brad

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Rao, Chandra

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Kemeny, Gabor

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Strickler, John H

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Abbruzzese, James L

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Harrison, Michael R

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Hsu, David S

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Healy, Patrick

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Li, Jing

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Pi, Cinthia

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Prendergast, Katherine M

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Hobbs, Carey

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Gemberling, Sarah

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George, Daniel J

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Hurwitz, Herbert I

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Connelly, Mark

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Garcia-Blanco, Mariano A

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Armstrong, Andrew J

dc.coverage.spatial

United States

dc.date.accessioned

2016-05-01T13:23:47Z

dc.date.issued

2016-06

dc.description.abstract

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.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/26951228

dc.identifier

1541-7786.MCR-16-0011

dc.identifier.eissn

1557-3125

dc.identifier.uri

https://hdl.handle.net/10161/11944

dc.language

eng

dc.publisher

American Association for Cancer Research (AACR)

dc.relation.ispartof

Mol Cancer Res

dc.relation.isversionof

10.1158/1541-7786.MCR-16-0011

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Zhang, Tian|0000-0001-8914-3531

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Strickler, John H|0000-0001-7579-1175

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Harrison, Michael R|0000-0003-3776-8892

duke.contributor.orcid

Armstrong, Andrew J|0000-0001-7012-1754

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/26951228

pubs.begin-page

539

pubs.end-page

547

pubs.issue

6

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Basic Science Departments

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Clinical Science Departments

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Duke

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Duke Cancer Institute

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Institutes and Centers

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Medicine

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Medicine, Medical Oncology

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Molecular Genetics and Microbiology

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Pharmacology & Cancer Biology

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School of Medicine

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Surgery

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Surgery, Vascular Surgery

pubs.publication-status

Published

pubs.volume

14

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