Comparative assessment of NOIR-SS and ddPCR for ctDNA detection of EGFR L858R mutations in advanced L858R-positive lung adenocarcinomas
Abstract Genotyping epidermal growth factor receptor (EGFR) is an essential process to indicate lung adenocarcinoma patients for the most appropriate treatment. Liquid biopsy using circulating tumor DNA (ctDNA) potentially complements the use of tumor tissue biopsy for identifying genotype-specific...
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Nature Portfolio
2021
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oai:doaj.org-article:eec1572886f54d0eab80cbef0c524f562021-12-02T17:56:56ZComparative assessment of NOIR-SS and ddPCR for ctDNA detection of EGFR L858R mutations in advanced L858R-positive lung adenocarcinomas10.1038/s41598-021-94592-92045-2322https://doaj.org/article/eec1572886f54d0eab80cbef0c524f562021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94592-9https://doaj.org/toc/2045-2322Abstract Genotyping epidermal growth factor receptor (EGFR) is an essential process to indicate lung adenocarcinoma patients for the most appropriate treatment. Liquid biopsy using circulating tumor DNA (ctDNA) potentially complements the use of tumor tissue biopsy for identifying genotype-specific mutations in cancer cells. We assessed the performance of a high-fidelity sequencing method that uses molecular barcodes called the nonoverlapping integrated read sequencing system (NOIR-SS) for detecting EGFR L858R-mutated alleles in 33 advanced or recurrent patients with L858R mutation-positive lung adenocarcinoma revealed by matched tissue biopsy. We compared NOIR-SS with site-specific droplet digital PCR (ddPCR), which was taken as the reference, in terms of sensitivity and ability to quantify L858R variant allele fractions (VAFs). NOIR-SS and ddPCR had sensitivities of 87.9% (29/33) and 78.8% (26/33) for detecting L858R alleles, respectively. The VAFs measured by each assay were strongly correlated. Notably, one specimen was positive with a VAF of 30.12% for NOIR-SS but marginally positive with that of 0.05% for ddPCR because of a previously poorly recognized mechanism: two-base substitution-induced L858R (c.2573_2574delinsGA). These results indicate that NOIR-SS is a useful method for detecting ctDNA, potentially overcoming a limitation of ddPCR which highly depends on the binding ability of primers to specific targeting sequences.Daisuke AkahoriYusuke InoueNaoki InuiMasato KarayamaHideki YasuiHironao HozumiYuzo SuzukiKazuki FuruhashiTomoyuki FujisawaNoriyuki EnomotoYutaro NakamuraTakafumi SudaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q |
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Medicine R Science Q Daisuke Akahori Yusuke Inoue Naoki Inui Masato Karayama Hideki Yasui Hironao Hozumi Yuzo Suzuki Kazuki Furuhashi Tomoyuki Fujisawa Noriyuki Enomoto Yutaro Nakamura Takafumi Suda Comparative assessment of NOIR-SS and ddPCR for ctDNA detection of EGFR L858R mutations in advanced L858R-positive lung adenocarcinomas |
| description |
Abstract Genotyping epidermal growth factor receptor (EGFR) is an essential process to indicate lung adenocarcinoma patients for the most appropriate treatment. Liquid biopsy using circulating tumor DNA (ctDNA) potentially complements the use of tumor tissue biopsy for identifying genotype-specific mutations in cancer cells. We assessed the performance of a high-fidelity sequencing method that uses molecular barcodes called the nonoverlapping integrated read sequencing system (NOIR-SS) for detecting EGFR L858R-mutated alleles in 33 advanced or recurrent patients with L858R mutation-positive lung adenocarcinoma revealed by matched tissue biopsy. We compared NOIR-SS with site-specific droplet digital PCR (ddPCR), which was taken as the reference, in terms of sensitivity and ability to quantify L858R variant allele fractions (VAFs). NOIR-SS and ddPCR had sensitivities of 87.9% (29/33) and 78.8% (26/33) for detecting L858R alleles, respectively. The VAFs measured by each assay were strongly correlated. Notably, one specimen was positive with a VAF of 30.12% for NOIR-SS but marginally positive with that of 0.05% for ddPCR because of a previously poorly recognized mechanism: two-base substitution-induced L858R (c.2573_2574delinsGA). These results indicate that NOIR-SS is a useful method for detecting ctDNA, potentially overcoming a limitation of ddPCR which highly depends on the binding ability of primers to specific targeting sequences. |
| format |
article |
| author |
Daisuke Akahori Yusuke Inoue Naoki Inui Masato Karayama Hideki Yasui Hironao Hozumi Yuzo Suzuki Kazuki Furuhashi Tomoyuki Fujisawa Noriyuki Enomoto Yutaro Nakamura Takafumi Suda |
| author_facet |
Daisuke Akahori Yusuke Inoue Naoki Inui Masato Karayama Hideki Yasui Hironao Hozumi Yuzo Suzuki Kazuki Furuhashi Tomoyuki Fujisawa Noriyuki Enomoto Yutaro Nakamura Takafumi Suda |
| author_sort |
Daisuke Akahori |
| title |
Comparative assessment of NOIR-SS and ddPCR for ctDNA detection of EGFR L858R mutations in advanced L858R-positive lung adenocarcinomas |
| title_short |
Comparative assessment of NOIR-SS and ddPCR for ctDNA detection of EGFR L858R mutations in advanced L858R-positive lung adenocarcinomas |
| title_full |
Comparative assessment of NOIR-SS and ddPCR for ctDNA detection of EGFR L858R mutations in advanced L858R-positive lung adenocarcinomas |
| title_fullStr |
Comparative assessment of NOIR-SS and ddPCR for ctDNA detection of EGFR L858R mutations in advanced L858R-positive lung adenocarcinomas |
| title_full_unstemmed |
Comparative assessment of NOIR-SS and ddPCR for ctDNA detection of EGFR L858R mutations in advanced L858R-positive lung adenocarcinomas |
| title_sort |
comparative assessment of noir-ss and ddpcr for ctdna detection of egfr l858r mutations in advanced l858r-positive lung adenocarcinomas |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/eec1572886f54d0eab80cbef0c524f56 |
| work_keys_str_mv |
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1718379082405642240 |