Predictive efficacy of low burden EGFR mutation detected by next-generation sequencing on response to EGFR tyrosine kinase inhibitors in non-small-cell lung carcinoma

Hye Sook Kim, Jae Sook Sung, Song Ju Yang, Nak Jung Kwon, LiHua Jin, Seung Tae Kim, Kyong Hwa Park, Sang Won Shin, Han Kyeom Kim, Jin Hyoung Kang, Jeong Oh Kim, Jae Yong Park, Jin Eun Choi, HyoungKyu Yoon, Chan Kwon Park, Kap Seok Yang, Jeong Sun Seo, Yeul Hong Kim

Research output: Contribution to journalArticle

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Abstract

Direct sequencing remains the most widely used method for the detection of epidermal growth factor receptor (EGFR) mutations in lung cancer; however, its relatively low sensitivity limits its clinical use. The objective of this study was to investigate the sensitivity of detecting an epidermal growth factor receptor (EGFR) mutation from peptide nucleic acidlocked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp and Ion Torrent Personal Genome Machine (PGM) techniques compared to that by direct sequencing. Furthermore, the predictive efficacy of EGFR mutations detected by PNA-LNA PCR clamp was evaluated. EGFR mutational status was assessed by direct sequencing, PNA-LNA PCR clamp, and Ion Torrent PGM in 57 patients with non-small cell lung cancer (NSCLC). We evaluated the predictive efficacy of PNA-LNA PCR clamp on the EGFR-TKI treatment in 36 patients with advanced NSCLC retrospectively. Compared to direct sequencing (16/57, 28.1%), PNA-LNA PCR clamp (27/57, 47.4%) and Ion Torrent PGM (26/57, 45.6%) detected more EGFR mutations. EGFR mutant patients had significantly longer progressive free survival (14.31 vs. 21.61 months, P = 0.003) than that of EGFR wild patients when tested with PNA-LNA PCR clamp. However, no difference in response rate to EGFR TKIs (75.0% vs. 82.4%, P = 0.195) or overall survival (34.39 vs. 44.10 months, P = 0.422) was observed between the EGFR mutations by direct sequencing or PNA-LNA PCR clamp. Our results demonstrate firstly that patients with EGFR mutations were detected more frequently by PNA-LNA PCR clamp and Ion Torrent PGM than those by direct sequencing. EGFR mutations detected by PNALNA PCR clamp may be as a predicative factor for EGFR TKI response in patients with NSCLC. Copyright:

Original languageEnglish
Article numbere81975
JournalPLoS One
Volume8
Issue number12
DOIs
Publication statusPublished - 2013 Dec 20

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
carcinoma
tyrosine
phosphotransferases (kinases)
Clamping devices
lungs
Cells
Polymerase chain reaction
mutation
Mutation
Nucleic Acids
nucleic acids
polymerase chain reaction
peptides
Polymerase Chain Reaction
Peptides
cells
lung neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Predictive efficacy of low burden EGFR mutation detected by next-generation sequencing on response to EGFR tyrosine kinase inhibitors in non-small-cell lung carcinoma. / Kim, Hye Sook; Sung, Jae Sook; Yang, Song Ju; Kwon, Nak Jung; Jin, LiHua; Kim, Seung Tae; Park, Kyong Hwa; Shin, Sang Won; Kim, Han Kyeom; Kang, Jin Hyoung; Kim, Jeong Oh; Park, Jae Yong; Choi, Jin Eun; Yoon, HyoungKyu; Park, Chan Kwon; Yang, Kap Seok; Seo, Jeong Sun; Kim, Yeul Hong.

In: PLoS One, Vol. 8, No. 12, e81975, 20.12.2013.

Research output: Contribution to journalArticle

Kim, Hye Sook ; Sung, Jae Sook ; Yang, Song Ju ; Kwon, Nak Jung ; Jin, LiHua ; Kim, Seung Tae ; Park, Kyong Hwa ; Shin, Sang Won ; Kim, Han Kyeom ; Kang, Jin Hyoung ; Kim, Jeong Oh ; Park, Jae Yong ; Choi, Jin Eun ; Yoon, HyoungKyu ; Park, Chan Kwon ; Yang, Kap Seok ; Seo, Jeong Sun ; Kim, Yeul Hong. / Predictive efficacy of low burden EGFR mutation detected by next-generation sequencing on response to EGFR tyrosine kinase inhibitors in non-small-cell lung carcinoma. In: PLoS One. 2013 ; Vol. 8, No. 12.
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abstract = "Direct sequencing remains the most widely used method for the detection of epidermal growth factor receptor (EGFR) mutations in lung cancer; however, its relatively low sensitivity limits its clinical use. The objective of this study was to investigate the sensitivity of detecting an epidermal growth factor receptor (EGFR) mutation from peptide nucleic acidlocked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp and Ion Torrent Personal Genome Machine (PGM) techniques compared to that by direct sequencing. Furthermore, the predictive efficacy of EGFR mutations detected by PNA-LNA PCR clamp was evaluated. EGFR mutational status was assessed by direct sequencing, PNA-LNA PCR clamp, and Ion Torrent PGM in 57 patients with non-small cell lung cancer (NSCLC). We evaluated the predictive efficacy of PNA-LNA PCR clamp on the EGFR-TKI treatment in 36 patients with advanced NSCLC retrospectively. Compared to direct sequencing (16/57, 28.1{\%}), PNA-LNA PCR clamp (27/57, 47.4{\%}) and Ion Torrent PGM (26/57, 45.6{\%}) detected more EGFR mutations. EGFR mutant patients had significantly longer progressive free survival (14.31 vs. 21.61 months, P = 0.003) than that of EGFR wild patients when tested with PNA-LNA PCR clamp. However, no difference in response rate to EGFR TKIs (75.0{\%} vs. 82.4{\%}, P = 0.195) or overall survival (34.39 vs. 44.10 months, P = 0.422) was observed between the EGFR mutations by direct sequencing or PNA-LNA PCR clamp. Our results demonstrate firstly that patients with EGFR mutations were detected more frequently by PNA-LNA PCR clamp and Ion Torrent PGM than those by direct sequencing. EGFR mutations detected by PNALNA PCR clamp may be as a predicative factor for EGFR TKI response in patients with NSCLC. Copyright:",
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