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01.12.2018 | Letter to the Editor | Ausgabe 1/2018 Open Access

Molecular Cancer 1/2018

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

Zeitschrift:
Molecular Cancer > Ausgabe 1/2018
Autoren:
Jae Young Hur, Hee Joung Kim, Jong Sik Lee, Chang-Min Choi, Jae Cheol Lee, Min Kyo Jung, Chan Gi Pack, Kye Young Lee
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12943-018-0772-6) contains supplementary material, which is available to authorized users.

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.
Zusatzmaterial
Additional file 1: Materials and methods. Table S1. Patient demographics and clinical characteristics. Table S2. Concentration and purity (260/280) of BALF EV DNA and BALF cfDNA. Table S3. Concentration of DNA larger than 1kb in EV DNA and cfDNA. Table S4. Ct value of EV DNA and cfDNA samples and their differences. Table S5. Comparison of the EGFR mutation status between tumor tissue and plasma in EGFR-TKIs naïve patients. Table S6. Clinical characteristics of patients who developed acquired resistance to 1st or 2nd generation EGFR-TKIs and underwent rebiopsy. Figure S1. Sizes of purified BALF EVs. Figure S2. Sizes of purified plasma EVs. Figure S3. EM image of BALF EVs. Figure S4. Immuno-EM images show detection of dsDNA in BALF EVs. Red arrows indicate gold particles. Figure S5. Gel-like images show the size and amount of EV DNA and cfDNA determined using the bioanalyzer. (DOCX 900 kb)
12943_2018_772_MOESM1_ESM.docx
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