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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Next-generation sequencing of tyrosine kinase inhibitor-resistant non-small-cell lung cancers in patients harboring epidermal growth factor-activating mutations

Authors: Katsuhiro Masago, Shiro Fujita, Miho Muraki, Akito Hata, Chiyuki Okuda, Kyoko Otsuka, Reiko Kaji, Jumpei Takeshita, Ryoji Kato, Nobuyuki Katakami, Yukio Hirata

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

The aim of this study was to detect the epidermal growth factor receptor (EGFR)-activating mutations and other oncogene alterations in patients with non-small-cell lung cancers (NSCLC) who experienced a treatment failure in response to EGFR-tyrosine kinase inhibitors (TKIs) with a next generation sequencer.

Methods

Fifteen patients with advanced NSCLC previously treated with EGFR-TKIs were examined between August 2005 and October 2014. For each case, new biopsies were performed, followed by DNA sequencing on an Ion Torrent Personal Genome Machine (PGM) system using the Ion AmpliSeq Cancer Hotspot Panel version 2.

Results

All 15 patients were diagnosed with NSCLC harboring EGFR-activating mutations (seven cases of exon 19 deletion, seven cases of L858R in exon 21, and one case of L861Q in exon 21). Of the 15 cases, acquired T790M resistance mutations were detected in 9 (60.0 %) patients. In addition, other mutations were identified outside of EGFR, including 13 cases (86.7 %) exhibiting TP53 P72R mutations, 5 cases (33.3 %) of KDR Q472H, and 2 cases (13.3 %) of KIT M541L.

Conclusions

Here, we showed that next-generation sequencing (NGS) is able to detect EGFR T790M mutations in cases not readily diagnosed by other conventional methods. Significant differences in the degree of EGFR T790M and other EGFR-activating mutations may be indicative of the heterogeneity of disease phenotype evident within these patients. The co-existence of known oncogenic mutations within each of these patients may play a role in acquired EGFR-TKIs resistance, suggesting the need for alternative treatment strategies, with PCR-based NGS playing an important role in disease diagnosis.
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Metadata
Title
Next-generation sequencing of tyrosine kinase inhibitor-resistant non-small-cell lung cancers in patients harboring epidermal growth factor-activating mutations
Authors
Katsuhiro Masago
Shiro Fujita
Miho Muraki
Akito Hata
Chiyuki Okuda
Kyoko Otsuka
Reiko Kaji
Jumpei Takeshita
Ryoji Kato
Nobuyuki Katakami
Yukio Hirata
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1925-2

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