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E. Sueoka
Author of
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-028 - Characteristics of Cell Free DNA in Lung Cancer Patients (ID 8316)
09:30 - 09:30 | Author(s): E. Sueoka
- Abstract
Background:
A third generation EGFR tyrosine kinase inhibitor, osimertinib, is effective for T790M positive lung cancer patients. Although the tissue re-biopsy of primary or metastatic tumors was required to use osimertinib, cell free DNA (cfDNA) has been recently approved for detection of T790M in Japan. We have reported that cfDNA size distribution was different between lung cancer and healthy individuals using a capillary electrophoresis system, that is one peak around the size of 170 bp in healthy individuals, and two peaks, 170 bp and 5 kb in advanced lung cancer patients. The purpose of this study is to clarify the clinical and biological characteristics of each sized cfDNA.
Method:
The plasma collected from 92 lung cancer patients, 18 benign pulmonary disease patients, 20 healthy individuals at Saga University Hospital were analyzed. cfDNA extraction was performed from 1000μl plasma by automated DNA extraction system using cellulose magnetic beads. We first compared the DNA concentrations and cfDNA size among three groups. The DNA concentrations were quantified by Quantus[®], the fluorescent measurement of dsDNA intercalated dye, and cfDNA size was analyzed by the Agilent 2100 Bioanalyzer[®]. We next separately isolated cfDNA 170 bp and 5 kb fragments, and detected the epidermal growth factor receptor (EGFR) L858R point mutation by mutation-biased PCR and quenched probe system (MBP-QP) method.
Result:
The DNA concentration was higher in lung cancer patients compared to those in benign pulmonary disease and healthy individuals. Divided by histological types, DNA concentrations were highest in small cell carcinoma, and were increased in patients with advanced stages. Especially, DNA concentrations were higher in presence of metastasis, and 5 kb fragments were significantly increased in these cases. L858R positive patients showed higher DNA concentration with more obvious difference in 5 kb fragments. L858R was detected in both cfDNA fragments, 170 bp and 5 kb, which were separately isolated, suggesting that both sized DNA fragments contain circulating tumor-derived DNA (ctDNA).
Conclusion:
cfDNA concentrations were associated with progression of lung cancers, and bimodal characteristic was observed in terms of cfDNA size. Although the 170 bp short fragments of cfDNA are well known as an apoptotic product, the origin of 5 kb long fragments is still unclear. We have continuously examined how ctDNA was released from tumor cell.
