scholarly journals Non-invasive diagnosis of early-stage lung cancer using high-throughput targeted DNA methylation sequencing of circulating tumor DNA (ctDNA)

Theranostics ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 2056-2070 ◽  
Author(s):  
Wenhua Liang ◽  
Yue Zhao ◽  
Weizhe Huang ◽  
Yangbin Gao ◽  
Weihong Xu ◽  
...  
2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14557-e14557
Author(s):  
Jong Ho Cho ◽  
Il-Jin Kim ◽  
Junghee Lee ◽  
Hong Kwan Kim ◽  
Jinseon Lee ◽  
...  

e14557 Background: Circulating tumor DNA (ctDNA) analysis has been successfully applied to therapy selection and treatment monitoring in advanced cancer patients. However, it is not yet established whether ctDNA can be used clinically for early cancer detection or predicting tumor recurrence in early stage lung cancer patients. Methods: We analyzed pre-operative plasma samples from 55 early stage NSCLC patients (stages I-IIIA) using next-generation sequencing to detect somatic mutations and differential epigenomics patterns, including methylation signatures. Results: Using somatic mutation analysis alone, ctDNA was detected in 42% (23/55) of patients, whereas combined mutational and epigenomic analysis detected ctDNA in 71%. ctDNA detection rate also varied markedly between lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC);using combined analysis of somatic mutations and epigenomic patterns, ctDNA was detected in all SCC patients, while only 55% of ADC (12/22) were ctDNA-positive (p= 0.006). Within the ADC subgroup, ctDNA detection rates using the combined approach were dependent on disease stage: 47% (8/17) in stage I, 100% (2/2) in stage II, and 100% (2/2) in stage IIIA. Importantly, pre-operative ctDNA status was correlated with tumor recurrence post-resection; three of eight (38%) ctDNA-positive stage I ADC patients recurred within 2 years of resection, while only one of nine (11%) ctDNA-negative stage I ADC patients recurred (p= 0.29). Conclusions: Taken together, we show that the combination of somatic mutation detection and epigenomic analysis outperforms each individual biomarker in the detection of ctDNA in early stage lung cancer. Importantly, we also demonstrate that pre-operative ctDNA detection may identify a high-risk population of early stage lung cancer patients that may benefit from (neo)adjuvant therapy.


2018 ◽  
Vol 9 (5) ◽  
pp. 509-515 ◽  
Author(s):  
Heng Zhao ◽  
Ke-Zhong Chen ◽  
Ben-Gang Hui ◽  
Kai Zhang ◽  
Fan Yang ◽  
...  

2017 ◽  
Vol 12 (1) ◽  
pp. S343-S344
Author(s):  
Michael Meyer ◽  
Timothy Bell ◽  
Daniel Sussman ◽  
David Wilbur ◽  
Chris Presley ◽  
...  

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