Abstract
Background/Aim: Patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) eventually develop resistance to these drugs. Although various mechanisms of such resistance have been identified, the mechanism in many cases remains unknown. Materials and Methods: Whole-exome sequencing was performed for tumor tissue from 15 patients with NSCLC who developed EGFR-TKI resistance. Tumor specimens obtained before EGFR-TKI treatment were also analyzed for four patients and normal white blood cell samples for six patients in order to detect genomic alterations that occurred during treatment. Results: The mutational signature and mutational load acquired during EGFR-TKI treatment varied among patients, with common EGFR-TKI resistance mechanisms including the T790M secondary mutation of EGFR and MET amplification being acquired together with many other genomic alterations. Our results provide insight into the mutational landscape acquired during the development of EGFR-TKI resistance in NSCLC.
| Original language | English |
|---|---|
| Pages (from-to) | 671-677 |
| Number of pages | 7 |
| Journal | Anticancer research |
| Volume | 39 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2019 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
Identification of genomic alterations acquired during treatment with EGFR-TKIs in non-small cell lung cancer. / Kubo, Naoki; Harada, Taishi; Shiraishi, Yoshimasa; Nosaki, Kaname; Nakagaki, Noriaki; Takeshita, Masafumi; Ouchi, Hiroshi; Iwama, Eiji; Tanaka, Kentaro; Okamoto, Isamu; Sasaki, Hiroyuki; Nakanishi, Yoichi.
In: Anticancer research, Vol. 39, No. 2, 01.02.2019, p. 671-677.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification of genomic alterations acquired during treatment with EGFR-TKIs in non-small cell lung cancer
AU - Kubo, Naoki
AU - Harada, Taishi
AU - Shiraishi, Yoshimasa
AU - Nosaki, Kaname
AU - Nakagaki, Noriaki
AU - Takeshita, Masafumi
AU - Ouchi, Hiroshi
AU - Iwama, Eiji
AU - Tanaka, Kentaro
AU - Okamoto, Isamu
AU - Sasaki, Hiroyuki
AU - Nakanishi, Yoichi
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Background/Aim: Patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) eventually develop resistance to these drugs. Although various mechanisms of such resistance have been identified, the mechanism in many cases remains unknown. Materials and Methods: Whole-exome sequencing was performed for tumor tissue from 15 patients with NSCLC who developed EGFR-TKI resistance. Tumor specimens obtained before EGFR-TKI treatment were also analyzed for four patients and normal white blood cell samples for six patients in order to detect genomic alterations that occurred during treatment. Results: The mutational signature and mutational load acquired during EGFR-TKI treatment varied among patients, with common EGFR-TKI resistance mechanisms including the T790M secondary mutation of EGFR and MET amplification being acquired together with many other genomic alterations. Our results provide insight into the mutational landscape acquired during the development of EGFR-TKI resistance in NSCLC.
AB - Background/Aim: Patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) eventually develop resistance to these drugs. Although various mechanisms of such resistance have been identified, the mechanism in many cases remains unknown. Materials and Methods: Whole-exome sequencing was performed for tumor tissue from 15 patients with NSCLC who developed EGFR-TKI resistance. Tumor specimens obtained before EGFR-TKI treatment were also analyzed for four patients and normal white blood cell samples for six patients in order to detect genomic alterations that occurred during treatment. Results: The mutational signature and mutational load acquired during EGFR-TKI treatment varied among patients, with common EGFR-TKI resistance mechanisms including the T790M secondary mutation of EGFR and MET amplification being acquired together with many other genomic alterations. Our results provide insight into the mutational landscape acquired during the development of EGFR-TKI resistance in NSCLC.
UR - http://www.scopus.com/inward/record.url?scp=85061015567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061015567&partnerID=8YFLogxK
U2 - 10.21873/anticanres.13162
DO - 10.21873/anticanres.13162
M3 - Article
VL - 39
SP - 671
EP - 677
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 2
ER -