Extracellular vesicle-derived DNA for performing EGFR genotyping of NSCLC patients

Mol Cancer. 2018 Jan 27;17(1):15. doi: 10.1186/s12943-018-0772-6.

Abstract

Tumor cells shed an abundance of extracellular vesicles (EVs) to body fluids containing bioactive molecules including DNA, RNA, and protein. Investigations in the field of tumor-derived EVs open a new horizon in understanding cancer biology and its potential as cancer biomarkers as well as platforms for personalized medicine. This study demonstrates that successfully isolated EVs from plasma and bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC) patients contain DNA that can be used for EGFR genotyping through liquid biopsy. In both plasma and BALF samples, liquid biopsy results using EV DNA show higher accordance with conventional tissue biopsy compared to the liquid biopsy of cfDNA. Especially, liquid biopsy with BALF EV DNA is tissue-specific and extremely sensitive compared to using cfDNA. Furthermore, use of BALF EV DNA also demonstrates higher efficiency in comparison to tissue rebiopsy for detecting p.T790 M mutation in the patients who developed resistance to EGFR-TKIs. These finding demonstrate possibility of liquid biopsy using EV DNA potentially replacing the current diagnostic methods for more accurate, cheaper, and faster results.

Keywords: Bronchoalveolar lavage fluid; EGFR mutant DNA; Extracellular vesicles; Liquid biopsy; Non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bronchoalveolar Lavage Fluid
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Circulating Tumor DNA
  • DNA, Neoplasm*
  • Drug Resistance, Neoplasm
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / ultrastructure
  • Genes, erbB-1*
  • Genetic Testing
  • Genotyping Techniques
  • Humans
  • Liquid Biopsy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mutation

Substances

  • Circulating Tumor DNA
  • DNA, Neoplasm