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

Zhang, Tian

Boominathan, Rengasamy

Foulk, Brad

Rao, Chandra

Kemeny, Gabor

Strickler, John H

Abbruzzese, James L

Harrison, Michael R

Hsu, David S

Healy, Patrick

Li, Jing

Pi, Cinthia

Prendergast, Katherine M

Hobbs, Carey

Gemberling, Sarah

George, Daniel J

Hurwitz, Herbert I

Connelly, Mark

Garcia-Blanco, Mariano A

Armstrong, Andrew J

United States

2016-05-01T13:23:47Z

2016-06

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.

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

1541-7786.MCR-16-0011

1557-3125

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

eng

American Association for Cancer Research (AACR)

Mol Cancer Res

10.1158/1541-7786.MCR-16-0011

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

Journal article

Zhang, Tian|0000-0001-8914-3531

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

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

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

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

539

547

6

Basic Science Departments

Clinical Science Departments

Duke

Duke Cancer Institute

Institutes and Centers

Medicine

Medicine, Medical Oncology

Molecular Genetics and Microbiology

Pharmacology & Cancer Biology

School of Medicine

Surgery

Surgery, Vascular Surgery

Published

14