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Quantification of mutant alleles in circulating tumor DNA can predict survival in lung cancer.


ABSTRACT: We aimed to investigate the feasibility of droplet digital PCR (ddPCR) for the quantitative and dynamic detection of EGFR mutations and next generation sequencing (NGS) for screening EGFR-tyrosine kinase inhibitors (EGFR-TKIs) resistance-relevant mutations in circulating tumor DNA (ctDNA) from advanced lung adenocarcinoma (ADC) patients.Detection limit of EGFR mutation in ctDNA by ddPCR was 0.04%. Taking the EGFR mutation in tumor tissue as the golden standard, the concordance of EGFR mutations detected in ctDNA was 74% (54/73). Patients with EGFR mutation in ctDNA (n = 54) superior progression-free survival (PFS, median, 12.6 vs. 6.7 months, P < 0.001) and overall survival (OS, median, 35.6 vs. 23.8 months, P = 0.028) compared to those with EGFR wild type in ctDNA (n = 19). Patients with high EGFR-mutated abundance in ctDNA (> 5.15%) showed better PFS compared to those with low EGFR mutated abundance (? 5.15%) (PFS, median, 15.4 vs. 11.1 months, P = 0.021). NGS results showed that 66.6% (8/12) total mutational copy number were elevated and 76.5% (26/34) mutual mutation frequency increased after disease progression.Seventy-three advanced ADC patients with tumor tissues carrying EGFR mutations and their matched pre- and post-EGFR-TKIs plasma samples were enrolled in this study. Absolute quantities of plasma EGFR mutant and wild-type alleles were measured by ddPCR. Multi-genes testing was performed using NGS in 12 patients.Dynamic and quantitative analysis of EGFR mutation in ctDNA could guide personalized therapy for advanced ADC. NGS shows good performance in multiple genes testing especially novel and uncommon genes.

SUBMITTER: Yang X 

PROVIDER: S-EPMC4991494 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Quantification of mutant alleles in circulating tumor DNA can predict survival in lung cancer.

Yang Xue X   Zhuo Minglei M   Ye Xin X   Bai Hua H   Wang Zhijie Z   Sun Yun Y   Zhao Jun J   An Tongtong T   Duan Jianchun J   Wu Meina M   Wang Jie J  

Oncotarget 20160401 15


<h4>Purpose</h4>We aimed to investigate the feasibility of droplet digital PCR (ddPCR) for the quantitative and dynamic detection of EGFR mutations and next generation sequencing (NGS) for screening EGFR-tyrosine kinase inhibitors (EGFR-TKIs) resistance-relevant mutations in circulating tumor DNA (ctDNA) from advanced lung adenocarcinoma (ADC) patients.<h4>Results</h4>Detection limit of EGFR mutation in ctDNA by ddPCR was 0.04%. Taking the EGFR mutation in tumor tissue as the golden standard, th  ...[more]

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