Circulating tumor DNA measurement provides reliable mutation detection in mice with human lung cancer xenografts

Laboratory Investigation; a Journal of Technical Methods and Pathology
Ling WeiXianrang Song

Abstract

Genotype-directed targeted therapy has become one of the standard treatment options for non-small cell lung cancer (NSCLC). There have been numerous limitations associated with mutation analysis of tissue samples. Consequently, mutational profile analysis of circulating cell-free DNA (cfDNA) by highly sensitive droplet digital PCR (ddPCR) assay has been developed. Possibly due to differences in cfDNA concentrations, previous studies have shown numerous discrepancies in mutation detection consistency between tissue and cfDNA. In order to rigorously analyze the amount of cfDNA needed, we constructed 72 athymic nude mice xenografted with NCI-H1975 (harboring a EGFR T790M mutation) or NCI-H460 (harboring a KRAS Q61H mutation) human NSCLC. We thoroughly investigated the relationship between plasma cfDNA using Q-PCR targeting human long interspersed nuclear element-1 (LINE-1) retrotransposon and the mouse ACTB gene, and the accuracy of mutation detection by ddPCR at different times post-graft. Our results show that the concentration and fragmentation of human (tumor) derived cfDNA (hctDNA) were positively correlated with tumor weight, but not with mouse-derived cfDNA (mcfDNA). Quantification of cfDNA by Q-PCR depends on the amplified...Continue Reading

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Citations

Feb 3, 2020·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Joana F MarquesJosé L Costa
Mar 14, 2021·Apoptosis : an International Journal on Programmed Cell Death·Atsushi MuraoPing Wang

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Methods Mentioned

BETA
PCR
xenografts
xenograft
biopsy

Software Mentioned

Quanta Soft

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