Application of Single-Molecule Amplification and Resequencing Technology for Broad Surveillance of Plasma Mutations in Patients with Advanced Lung Adenocarcinoma.

Wang Z1, Cheng G2, Han X3, Mu X4, Zhang Y5, Cui D1, Liu C6, Zhang L7, Fan Z8, Ma L9, Yang L1, Di J1, Cram DS10, Shi Y11, Liu D12.

Author information

Abstract

Liquid biopsy to access the circulating tumor DNA is a promising surrogate for invasive tumor genotyping. We designed a multiplex assay based on circulating single-molecule amplification and resequencing technology (cSMART) to simultaneously detect and quantitate hot spot EGFR, KRAS, BRAF, ERBB2, and ALK plasma DNA variants in 103 patients with advanced lung adenocarcinoma. In validation studies using an analytical mutation standard, the sensitivity of the assay for EGFR mutation detection was at least 0.1% and specificity was 100%. The diagnostic detection sensitivity was one mutant molecule per 2 mL of plasma. The most frequently detected plasma mutations were EGFR variants L858R (21.4%), exon 19 deletions (19.4%), T790M (9.7%), and KRAS G12X variants (9.7%). Rarer were BRAF V600X (1.95%) and ERBB2 exon 20 (0.97%) variants. In single samples, four novel EGFR exon 19 deletions, one KIF5B-ALK, and two EML4-ALK variants were also detected. From comparisons of 103 matched plasma and tumor specimen genotypes, 75 (72.8%) were concordant, 9 (8.8%) were partially concordant, and 19 (18.4%) were discordant. Overall, the combined positive and negative concordance rate for detection of each oncogenic variant exceeded 90%. On the basis of these findings, we propose that cSMART displays the diagnostic hallmarks of a comprehensive plasma genotyping assay, with potential application for precisely monitoring changes in plasma mutation levels in response to targeted drug therapy.

PMID:: 27870944
DOI:: 10.1016/j.jmoldx.2016.09.008

From HuGE Literature Finder Database

This database contains published literature on genetic associations and other human genome epidemiology

Application of Single-Molecule Amplification and Resequencing Technology for Broad Surveillance of Plasma Mutations in Patients with Advanced Lung Adenocarcinoma.
The Journal of molecular diagnostics : JMD 2017 Jan 19 (1): 169-181.
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