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

Matteo Turetta1, Michela Bulfoni2, Giulia Brisotto3,4,5

  • 1Department of Medicine, University of Udine, P.le Kolbe 4, 33100 Udine, Italy. matteo.turetta@uniud.it.

Cancers
|August 17, 2018
PubMed

Insights

This study identifies hypermetabolic circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) patients. These cells can be analyzed for mutations, aiding in therapy selection and revealing tumor heterogeneity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Molecular characterization is crucial for non-small cell lung cancer (NSCLC) therapy selection.
  • Circulating tumor cells (CTCs) offer potential for molecular analysis, but current technologies face limitations.

Purpose of the Study:

  • To assess the mutational status of NSCLC using hypermetabolic CTCs detected by their glucose uptake.
  • To validate a method for enriching and analyzing CTCs for EGFR and KRAS mutations.

Main Methods:

  • Peripheral blood samples from 30 Stage IV NSCLC patients were incubated with a fluorescent glucose analog (2-NBDG).
  • Hypermetabolic CTCs were sorted using flow cytometry based on high glucose uptake.
  • EGFR and KRAS mutations in sorted CTCs were detected using droplet digital PCR (ddPCR).

Main Results:

  • Mutated DNA was detected in 85% of sorted CTCs, with 70% matching the primary tumor's mutations.
  • New mutations (EGFR p.746_750del, KRAS p.G12V) were identified in patients with wild-type primary tumors.
  • Multiple KRAS mutations were found in two patients, and discordant mutations were observed in two others.

Conclusions:

  • Hypermetabolic CTCs can be enriched without specialized equipment and their mutational status successfully assessed by ddPCR.
  • This method facilitates non-small cell lung cancer (NSCLC) molecular profiling and therapy selection.
  • The detection of novel mutations in CTCs highlights their utility in probing tumor heterogeneity.
Keywords:
CTCglucose uptakeliquid biopsymetabolismnon-small cell lung cancer

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