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A Comparison of ddPCR and ARMS for detecting EGFR T790M status in ctDNA from advanced NSCLC patients with acquired EGFR‐TKI resistance
Author(s) -
Wang Wenxian,
Song Zhengbo,
Zhang Yiping
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.978
Subject(s) - t790m , digital polymerase chain reaction , liquid biopsy , mutation , medicine , epidermal growth factor receptor , lung cancer , resistance mutation , acquired resistance , cancer , pathology , cancer research , oncology , polymerase chain reaction , biology , gene , gefitinib , genetics , reverse transcriptase
A sensitive and convenient method for detecting epidermal growth factor receptor ( EGFR ) T790M mutations from circulating tumor DNA (ct DNA ) in advanced non–small cell lung cancer ( NSCLC ) patients with acquired EGFR ‐ TKI resistance would be desirable to direct patient sequential treatment strategy. A comparison of two platforms for detecting EGFR mutations in plasma ct DNA was undertaken. Plasma samples and tumor samples were collected from patients with acquired EGFR ‐ TKI resistance in Zhejiang Cancer Hospital from December 2014 to December 2015. Extracted ct DNA was analyzed using two platforms (Droplet Digital PCR and ARMS [ dPCR ]). A total of 108 patients were enrolled in this study. One hundred and eight patient plasma samples were detected by dd PCR and 75 were detected by ARMS . And 16 patients obtained tissue re‐biopsy, using ARMS assay for detecting EGFR T790M mutation. In all, 43.7% (47/108) had acquired T790M mutation by dd PCR . In 75 patient plasma samples, comparing dd PCR with ARMS , the rates of T790M mutation were 46.7% (35/75) and 25.3% (19/75) by dd PCR and ARMS , respectively. Of all, 16 patients both had tumor and plasma samples, the T790M mutation rates were 56.3% (9/16) by ARMS in tissue and 50.5% (8/16) by dd PCR in plasma ct DNA . The progression mode tended to gradual progression in T790M mutation patients (40.4%), but the T790M negative was inclined to the mode of dramatic progression (39.3%). The patients with T790M‐positive tumors had a longer time to disease progression after treatment with EGFR ‐ TKI s (median, 13.1 months vs. 10.8 months; P  = 0.010) and overall survival (median, 35.3 months vs. 30.3 months; P  = 0.214) compared with those with T790M‐negative patients. Our study demonstrates ddPCR assay may provide a highly sensitive method to detect EGFR T790M gene in plasma. And T790M‐positive patients have better clinical outcomes to EGFR ‐ TKI s than T790M‐negative patients.

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