Identification of Circulating Tumor DNA for the Early Detection of Small-cell Lung Cancer

EBioMedicine. 2016 Aug;10:117-23. doi: 10.1016/j.ebiom.2016.06.032. Epub 2016 Jun 25.


Circulating tumor DNA (ctDNA) is emerging as a key potential biomarker for post-diagnosis surveillance but it may also play a crucial role in the detection of pre-clinical cancer. Small-cell lung cancer (SCLC) is an excellent candidate for early detection given there are no successful therapeutic options for late-stage disease, and it displays almost universal inactivation of TP53. We assessed the presence of TP53 mutations in the cell-free DNA (cfDNA) extracted from the plasma of 51 SCLC cases and 123 non-cancer controls. We identified mutations using a pipeline specifically designed to accurately detect variants at very low fractions. We detected TP53 mutations in the cfDNA of 49% SCLC patients and 11.4% of non-cancer controls. When stratifying the 51 initial SCLC cases by stage, TP53 mutations were detected in the cfDNA of 35.7% early-stage and 54.1% late-stage SCLC patients. The results in the controls were further replicated in 10.8% of an independent series of 102 non-cancer controls. The detection of TP53 mutations in 11% of the 225 non-cancer controls suggests that somatic mutations in cfDNA among individuals without any cancer diagnosis is a common occurrence, and poses serious challenges for the development of ctDNA screening tests.

Keywords: Early detection; Screening; Small-cell lung cancer; TP53 mutations; cfDNA; ctDNA.

MeSH terms

  • Biomarkers, Tumor*
  • Case-Control Studies
  • DNA, Neoplasm* / blood
  • Early Detection of Cancer
  • Female
  • Humans
  • Leukocytes / metabolism
  • Lung Neoplasms / blood
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics*
  • Male
  • Mutation
  • Neoplasm Staging
  • Small Cell Lung Carcinoma / blood
  • Small Cell Lung Carcinoma / diagnosis*
  • Small Cell Lung Carcinoma / genetics*
  • Tumor Suppressor Protein p53 / genetics


  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Tumor Suppressor Protein p53