Assessment of the mutational status of NSCLC using hypermetabolic circulating tumor cells

Matteo Turetta, Michela Bulfoni, Giulia Brisotto, Gianpiero Fasola, Andrea Zanello, Eva Biscontin, Laura Mariuzzi, Agostino Steffan, Carla Di Loreto, Daniela Cesselli, Fabio Del Ben

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number270
JournalCancers
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 14 2018

Keywords

  • CTC
  • Glucose uptake
  • Liquid biopsy
  • Metabolism
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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