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Updated: Apr 15, 2026

A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction
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High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer

E Pailler1, N Auger2, C R Lindsay1

  • 1INSERM U981 "Identification of Molecular Predictors and new Targets for Cancer Treatment", University of Paris-Sud XI, Gustave Roussy, Villejuif Translational Research Laboratory, Gustave Roussy, Villejuif.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|April 8, 2015
PubMed
Abstract

Insights

Circulating tumor cells (CTCs) can detect ROS1 rearrangements in non-small-cell lung cancer (NSCLC). CTCs exhibit genetic heterogeneity and chromosomal instability, potentially explaining resistance to targeted therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Genetic aberrations in the ROS1 gene are found in a subset of non-small-cell lung cancer (NSCLC) patients.
  • ROS1 rearrangements can drive tumor growth and are targets for specific therapies like crizotinib.

Purpose of the Study:

  • To determine if ROS1 rearrangements can be detected in circulating tumor cells (CTCs) from NSCLC patients.
  • To investigate tumor heterogeneity in CTCs and tumor biopsies of ROS1-rearranged NSCLC patients.
  • To assess chromosomal instability in CTCs.

Main Methods:

  • Isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH) were used to detect ROS1 rearrangement in CTCs.
  • ROS1 gene alterations in CTCs and tumor biopsies were compared.
  • Numerical chromosomal instability (CIN) in CTCs was assessed via DNA content and chromosome enumeration.

Main Results:

  • ROS1 rearrangement was detected in CTCs of all four ROS1-rearranged NSCLC patients.
  • Baseline CTCs from ROS1-rearranged patients showed significantly higher tumor heterogeneity compared to tumor biopsies.
  • CTCs exhibited high DNA content and chromosome gain, indicating significant numerical CIN.

Conclusions:

  • This study demonstrates the feasibility of using CTCs for noninvasive detection of ROS1 rearrangement in NSCLC.
  • CTCs from ROS1-rearranged NSCLC patients display significant heterogeneity and elevated numerical CIN.
  • This heterogeneity and CIN in CTCs may represent a mechanism for escaping ROS1-inhibitor therapy.
Keywords:
FA-FISHROS1-rearranged non-small-cell lung cancercirculating tumor cellsfiltration enrichmentpredictive biomarker

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