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

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 growt...

Full description

Bibliographic Details
Main Authors: 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
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869671/
id pubmed-3869671
recordtype oai_dc
spelling pubmed-38696712013-12-27 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 Research Article 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 acid-locked 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 PNA-LNA PCR clamp may be as a predicative factor for EGFR TKI response in patients with NSCLC. Public Library of Science 2013-12-20 /pmc/articles/PMC3869671/ /pubmed/24376508 http://dx.doi.org/10.1371/journal.pone.0081975 Text en © 2013 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author 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
spellingShingle 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
author_facet 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
author_sort Kim, Hye Sook
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
description 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 acid-locked 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 PNA-LNA PCR clamp may be as a predicative factor for EGFR TKI response in patients with NSCLC.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869671/
_version_ 1612040377846464512