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Cancers 2018, 10(8), 270; https://doi.org/10.3390/cancers10080270

Assessment of the Mutational Status of NSCLC Using Hypermetabolic Circulating Tumor Cells

1
Department of Medicine, University of Udine, P.le Kolbe 4, 33100 Udine, Italy
2
Immunopathology and Cancer Biomarkers, C.R.O. Aviano National Cancer Institute IRCCS, via F. Gallini 2, 33081 Aviano (PN), Italy
3
IOV-IRCCS, Immunology and Molecular Oncology Unit, V. Gattamelata 64, 35128 Padova, Italy
4
DISCOG, University of Padova, V. Giustiniani 2, 35128 Padova, Italy
5
Udine Academic Hospital, P.le Santa Maria della Misericordia 15, 33100 Udine, Italy
These authors contributed equally to the work.
*
Authors to whom correspondence should be addressed.
Received: 28 May 2018 / Revised: 1 August 2018 / Accepted: 10 August 2018 / Published: 14 August 2018
(This article belongs to the Special Issue Circulating Tumor Cells (CTCs))
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Abstract

Molecular characterization is currently a key step in NSCLC therapy selection. Circulating tumor cells (CTC) are excellent candidates for downstream analysis, but technology is still lagging behind. In this work, we show that the mutational status of NSCLC can be assessed on hypermetabolic CTC, detected by their increased glucose uptake. We validated the method in 30 Stage IV NSCLC patients: peripheral blood samples were incubated with a fluorescent glucose analog (2-NBDG) and analyzed by flow cytometry. Cells with the highest glucose uptake were sorted out. EGFR and KRAS mutations were detected by ddPCR. In sorted cells, mutated DNA was found in 85% of patients, finding an exact match with primary tumor in 70% of cases. Interestingly, in two patients multiple KRAS mutations were detected. Two patients displayed different mutations with respect to the primary tumor, and in two out of the four patients with a wild type primary tumor, new mutations were highlighted: EGFR p.746_750del and KRAS p.G12V. Hypermetabolic CTC can be enriched without the need of dedicated equipment and their mutational status can successfully be assessed by ddPCR. Finally, the finding of new mutations supports the possibility of probing tumor heterogeneity. View Full-Text
Keywords: CTC; metabolism; glucose uptake; non-small cell lung cancer; liquid biopsy CTC; metabolism; glucose uptake; non-small cell lung cancer; liquid biopsy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Turetta, M.; Bulfoni, M.; Brisotto, G.; Fasola, G.; Zanello, A.; Biscontin, E.; Mariuzzi, L.; Steffan, A.; Di Loreto, C.; Cesselli, D.; Del Ben, F. Assessment of the Mutational Status of NSCLC Using Hypermetabolic Circulating Tumor Cells. Cancers 2018, 10, 270.

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