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

Publication ,  Journal Article
Zhang, T; Boominathan, R; Foulk, B; Rao, C; Kemeny, G; Strickler, JH; Abbruzzese, JL; Harrison, MR; Hsu, DS; Healy, P; Li, J; Pi, C; Hobbs, C ...
Published in: Mol Cancer Res
June 2016

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.

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Published In

Mol Cancer Res

DOI

EISSN

1557-3125

Publication Date

June 2016

Volume

14

Issue

6

Start / End Page

539 / 547

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins c-met
  • Prospective Studies
  • Pilot Projects
  • Oncology & Carcinogenesis
  • Neoplastic Cells, Circulating
  • Immunomagnetic Separation
  • Humans
  • Feasibility Studies
  • Developmental Biology
  • Colorectal Neoplasms
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, T., Boominathan, R., Foulk, B., Rao, C., Kemeny, G., Strickler, J. H., … Armstrong, A. J. (2016). Development of a Novel c-MET-Based CTC Detection Platform. Mol Cancer Res, 14(6), 539–547. https://doi.org/10.1158/1541-7786.MCR-16-0011
Zhang, Tian, Rengasamy Boominathan, Brad Foulk, Chandra Rao, Gabor Kemeny, John H. Strickler, James L. Abbruzzese, et al. “Development of a Novel c-MET-Based CTC Detection Platform.Mol Cancer Res 14, no. 6 (June 2016): 539–47. https://doi.org/10.1158/1541-7786.MCR-16-0011.
Zhang T, Boominathan R, Foulk B, Rao C, Kemeny G, Strickler JH, et al. Development of a Novel c-MET-Based CTC Detection Platform. Mol Cancer Res. 2016 Jun;14(6):539–47.
Zhang, Tian, et al. “Development of a Novel c-MET-Based CTC Detection Platform.Mol Cancer Res, vol. 14, no. 6, June 2016, pp. 539–47. Pubmed, doi:10.1158/1541-7786.MCR-16-0011.
Zhang T, Boominathan R, Foulk B, Rao C, Kemeny G, Strickler JH, Abbruzzese JL, Harrison MR, Hsu DS, Healy P, Li J, Pi C, Prendergast KM, Hobbs C, Gemberling S, George DJ, Hurwitz HI, Connelly M, Garcia-Blanco MA, Armstrong AJ. Development of a Novel c-MET-Based CTC Detection Platform. Mol Cancer Res. 2016 Jun;14(6):539–547.

Published In

Mol Cancer Res

DOI

EISSN

1557-3125

Publication Date

June 2016

Volume

14

Issue

6

Start / End Page

539 / 547

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins c-met
  • Prospective Studies
  • Pilot Projects
  • Oncology & Carcinogenesis
  • Neoplastic Cells, Circulating
  • Immunomagnetic Separation
  • Humans
  • Feasibility Studies
  • Developmental Biology
  • Colorectal Neoplasms