Identification of small and non-small cell lung cancer markers in peripheral blood using cytokinesis-blocked micronucleus and spectral karyotyping assays

Randa A. El-Zein, Shereen Abdel-Rahman, Kyle J. Santee, Robert Yu, Sanjay Shete

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer. There is an urgent need to develop tools to identify individuals at high risk of developing SCLC. We have previously reported that the cytokinesis-blocked micronucleus (CBMN) assay is a strong predictor of non-small cell lung cancer (NSCLC). Here, we investigate the sensitivity of the CBMN endpoints as predictors of SCLC risk. We conducted the CBMN assay on SCLC patients (n = 216), NSCLC patients (n = 173), and healthy controls (n = 204). Per sample, 1,000 binucleated cells (BN) were scored, and 3 endpoints, micronuclei (BN-MN), nucleoplasmic bridges (BN-NPB), and nuclear buds(BN-BUD), were recorded. Spectral karyotyping was also conducted on SCLC patients (n = 116) and NSCLC patients (n = 137) to identify genomic regions unique to each disease. Significantly higher levels of CBMN endpoints were observed in both cancer groups compared to controls. BN-NPBs were significantly higher among SCLC patients compared to NSCLC patients (p < 0.001). Chromosomes 5 and 17 were associated with BN-MN, and chromosomes 5, 18, 20, and 22 were associated with BN-NPBs in SCLC patients. Given the high frequency of chromosome aberrations observed in SCLC, events such as reinsertion of the micronucleus and chromothripsis may be potential mechanisms for the genetic instability in these patients.

Original languageEnglish (US)
Pages (from-to)122-131
Number of pages10
JournalCytogenetic and Genome Research
Volume152
Issue number3
DOIs
StatePublished - Oct 1 2017

Keywords

  • Cytokinesis-blocked micronucleus assay
  • Genetic instability
  • Non-small cell lung cancer
  • Small cell lung cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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