Detection of breast cancer stem cell gene mutations in circulating free DNA during the evolution of metastases

Breast Cancer Res Treat. 2019 Nov;178(2):251-261. doi: 10.1007/s10549-019-05374-x. Epub 2019 Aug 6.

Abstract

Purpose: Limited knowledge exists on the detection of breast cancer stem cell (BCSC)-related mutations in circulating free DNA (cfDNA) from patients with advanced cancers. Identification of new cancer biomarkers may allow for earlier detection of disease progression and treatment strategy modifications.

Methods: We conducted a prospective study to determine the feasibility and prognostic utility of droplet digital polymerase chain reaction (ddPCR)-based BCSC gene mutation analysis of cfDNA in patients with breast cancer.

Results: Detection of quantitative BCSC gene mutation in cfDNA by ddPCR mirrors disease progression and thus may represent a valuable and cost-effective measure of tumor burden. We have previously shown that hematological and neurological expressed 1-like (HN1L), ribosomal protein L39 (RPL39), and myeloid leukemia factor 2 (MLF2) are novel targets for BCSC self-renewal, and targeting these genetic alterations could be useful for personalized genomic-based therapy.

Conclusion: BCSC mutation detection in cfDNA may have important implications for diagnosis, prognosis, and serial monitoring.

Keywords: Breast carcinoma; Droplet digital polymerase chain reaction; Metastasis; Mutation; Stem cell.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor*
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cell Transformation, Neoplastic / genetics*
  • Circulating Tumor DNA*
  • DNA Mutational Analysis
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Mutation*
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplastic Stem Cells / metabolism*
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA