domingo, 12 de marzo de 2017

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

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



 2017 Jan;19(1):169-181. doi: 10.1016/j.jmoldx.2016.09.008. Epub 2016 Nov 19.

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

Wang Z1Cheng G2Han X3Mu X4Zhang Y5Cui D1Liu C6Zhang L7Fan Z8Ma L9Yang L1Di J1Cram DS10Shi Y11Liu D12.

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

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